Strong dependence, both physiological and emotional, upon morphine.
The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.
Agents inhibiting the effect of narcotics on the central nervous system.
Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.
A plant genus of the family ASTERACEAE. M. chamomilla appears similar to Anthemis but this flower disk is conical and hollow and lacks chaffy bract scales and the odor is weaker. The common name of 'manzanilla' is confused with other meanings of the word. 'Matricaria chamomilla sensu' is classified by some as Tripleurospermum perforata. Other plants with similar common names include CHAMAEMELUM; TRIPLEUROSPERMUM and ANTHEMIS.
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
Analogs or derivatives of morphine.
The observable response an animal makes to any situation.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

Recent progress in the neurotoxicology of natural drugs associated with dependence or addiction, their endogenous agonists and receptors. (1/330)

Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine in opium are well known as drugs associated with dependence or addiction. Endogenous active substances that mimic the effects of the natural drugs and their respective receptors have been found in the mammalian central nervous system (CNS). Such active substances and receptors include acetylcholine (ACh) and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta 9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine, respectively. Considerable progress has been made in studies on neurotoxicity, in terms of the habituation, dependence and withdrawal phenomena associated with these drugs and with respect to correlations with endogenous active substances and their receptors. In this article we shall review recent findings related to the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients, nicotine, delta 9-THC and morphine in relation to their respective endogenous agents and receptors in the CNS.  (+info)

Modification of the expression of naloxone-precipitated withdrawal signs in morphine-dependent mice by diabetes: possible involvement of protein kinase C. (2/330)

The involvement of cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) in the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes was examined. Naloxone-precipitated withdrawal jumps were significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. I.c.v. pretreatment with either calphostin C, a PKC inhibitor, or KT-5720, a PKA inhibitor, attenuated naloxone-precipitated withdrawal jumps in morphine-dependent non-diabetic mice. However, naloxone-precipitated withdrawal jumps in morphine-dependent diabetic mice were not attenuated by i.c.v. pretreatment with either calphostin C or KT5720. Moreover, i.c.v. pretreatment with phorbol-12,13-dibutyrate (PDBu), a PKC activator, attenuated naloxone-precipitated withdrawal jumps in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice. The noradrenaline (NA) turnover in the frontal cortex in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was significantly increased 5 min after administration of naloxone. Naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was blocked by i.c.v. pretreatment with either calphostin C or KT5720 1 hr before naloxone challenge and blocked by PDBu 1 hr before the last injection of morphine. These results suggest that the co-activation of PKC and PKA is needed to elicit naloxone-precipitated withdrawal jumps and enhancement of turnover rate of NA in the frontal cortex in morphine-dependent non-diabetic mice. Furthermore, the attenuation of naloxone-precipitated withdrawal jumps in morphine-dependent diabetic mice may be due, in part, to the desensitization of mu-opioid receptors by the activation of PKC.  (+info)

Inhibition of calcium/calmodulin-dependent protein kinase II in rat hippocampus attenuates morphine tolerance and dependence. (3/330)

Learning and memory have been suggested to be important in the development of opiate addiction. Based on the recent findings that calcium/calmodulin-dependent protein kinase II (CaMKII) is essential in learning and memory processes, and morphine treatment increases CaMKII activity in hippocampus, the present study was undertaken to examine whether inhibition of hippocampal CaMKII prevents morphine tolerance and dependence. Here, we report that inhibition of CaMKII by intrahippocampal dentate gyrus administration of the specific inhibitors KN-62 and KN-93 to rats significantly attenuated the tolerance to the analgesic effect of morphine and the abstinence syndrome precipitated by opiate antagonist naloxone. In contrast, both KN-04 and KN-92, the inactive structural analogs of KN-62 and KN-93, failed to attenuate morphine tolerance and dependence, indicating that the observed effects of KN-62 and KN-93 are mediated through inhibition of CaMKII. Furthermore, administration of CaMKII antisense oligonucleotide into rat hippocampal dentate gyrus, which decreased the expression of CaMKII specifically, also attenuated morphine tolerance and dependence, while the corresponding sense oligonucleotide of CaMKII did not exhibit such inhibitory effect. Moreover, the KN-62 treatment abolished the rewarding properties of morphine as measured by the conditioned place preference. These results suggest that hippocampal CaMKII is critically involved in the development of morphine tolerance and dependence, and inhibition of this kinase may have some therapeutic benefit in the treatment of opiate tolerance and dependence.  (+info)

Total neurochemical lesion of noradrenergic neurons of the locus ceruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal. (4/330)

It has been suggested that an increase firing rate of noradrenergic neurons of the locus ceruleus is responsible for the opiate withdrawal syndrome. However, lesion studies have indicated that the noradrenergic neurons of the locus ceruleus are not essential for either the expression or suppression by clonidine of opiate withdrawal. The present study was designed to determine the effect of the almost complete 6-hydroxydopamine lesion of noradrenergic neurons (94%) of the locus ceruleus on various components of the opiate withdrawal syndrome and on its protection by clonidine. Morphine dependence was induced by s.c. implantation of morphine pellets (2 x 75 mg base). The following paradigms were used: 1) naloxone-induced conditioned place aversion, 2) naloxone-precipitated acute opiate withdrawal syndrome, 3) nycthemeral locomotor activity as a measure of spontaneous opiate withdrawal. The results showed that quasi-total lesion of noradrenergic neurons of the locus ceruleus did not modify opiate dependence as revealed by naloxone-induced conditioned place aversion and the expression of an acute morphine withdrawal syndrome. Moreover, clonidine prevented the opiate withdrawal syndrome in both lesioned and sham-operated rats, suggesting that the action of clonidine is certainly mediated through postsynaptic alpha(2)-adrenoceptor stimulation. Finally, the nycthemeral locomotor activity during spontaneous morphine withdrawal did not differ between the lesioned and the sham-operated rats.  (+info)

Levels of immunoreactive dynorphin A1-13 during development of morphine dependence in rats. (5/330)

AIM: To study the relationship between the levels of immunoreactive dynorphin A1-13 (ir-dynorphin A1-13) and the degree of morphine dependence. METHODS: The levels of ir-dynorphin A1-13 in discrete brain regions, spinal cord, and plasma in rats were determined by radioimmunoassay, and the degree of morphine dependence was assessed by scoring withdrawal signs on d 3, d 6, and d 12. RESULTS: Morphine injection s.c. decreased the levels of ir-dynorphin A1-13 in spinal cord, pituitary, and plasma. The levels of ir-dynorphin A1-13 in hippocampus and hypothalamus were increased. No changes in cortex, midbrain, cerebellum, pons, and medulla were observed. With continuous injection of morphine, withdrawal signs scores were increased on d 6, but there was no difference between the scores of d 6 and d 12. CONCLUSION: The changes of the levels of endogenous ir-dynorphin A1-13 in pituitary, spinal cord, and plasma were compatible with the degree of morphine dependence.  (+info)

Agmatine inhibited tolerance to and dependence on morphine in guinea pig ileum in vitro. (6/330)

AIM: To observe effect of agmatine (Agm) on tolerance to and substance dependence on morphine (Mor) in guinea pig ileum longitudinal muscle (GPILM). METHODS: The experiment was performed in electric field stimulation (EFS) test in vitro. RESULTS: Mor inhibited twitch contractions of GPILM induced by EFS [IC50 = 140 (107-182) nmol.L-1]. Incubation of GPILM with Mor 270 nmol.L-1 for 8 h evoked a 37-fold increase in IC50 of Mor (tolerance) and a contractile response to naloxone (Nal, substance dependence). When the preparations were coincubated with Mor + Nal and Mor + Agm, Mor lost the ability to induce tolerance and inhibited the contractile responses of the preparations to Nal by 90% and 75%, respectively. These effects of Agm could be almost completely antagonized by idazoxan. CONCLUSION: Agm prevented the development of tolerance to and substance dependence on Mor in GPILM in vitro by activation of imidazoline receptors.  (+info)

Effects of agmatine on tolerance to and substance dependence on morphine in mice. (7/330)

AIM: To study the effects of agmatine on tolerance to and dependence on morphine. METHODS: Inhibitory effects of agmatine on tolerance to and substance dependence on morphine were observed in mouse tolerant models and in mouse jumping test, respectively. RESULTS: Agmatine 0.125-2.5 mg.kg-1 prevented the development of tolerant to morphine in a dose-dependent manner. Pretreatment of mice with morphine induced an over 3-fold increase in analgesic ED50 (20.1, 14.4-28.0 mg.kg-1) than those with normal saline (6.3, 5.1-7.8 mg.kg-1). Pretreatment of mice with both of agmatine and morphine made morphine loss the ability to induce tolerance. Withdrawal jumps and loss in body weight induced by naloxone in morphine-dependent mice were prevented by agmatine (2.5-10 mg.kg-1) in a dose-dependent manner. ED50 of naloxone (21.4, 18.4-24 mg.kg-1) required to precipitate withdrawal jumps in mice pretreated with both agmatine and morphine was 8 times higher than that with morphine alone (2.5, 2.1-2.8 mg.kg-1). These effects of agmatine were blocked by idazoxan. CONCLUSION: Agmatine prevented tolerance to and substance dependence on morphine in mice by activation of imidazoline receptors.  (+info)

Correlation between inhibitions of morphine withdrawal and nitric-oxide synthase by agmatine. (8/330)

AIM: To study correlation between inhibitions of naloxone-precipitated withdrawal jumps and nitric-oxide synthase (NOS) activity by agmatine. METHODS: NOS activities in mouse brain were measured by determination of concentration of [3H]citrulline, the product of [3H]arginine. RESULTS: Agmatine inhibited NOS activity in naive and morphine-dependent mouse cerebellum, forebrain, and thalamus in substrate-competitive manner in vitro. Naloxone induced withdrawal jumps and an increase in NOS activity in cerebellum, forebrain, and thalamus of abstinent mice. Pretreatment of mice with morphine plus agmatine inhibited the effect of naloxone to precipitate withdrawal jumps and increase in NOS activity. The effect of agmatine was blocked by idazoxan. CONCLUSION: The inhibitory effect of agmatine on naloxone-precipitated withdrawal jumps is related to its inhibition of NOS activity by substrate competitive manner and activation of imidazoline receptors.  (+info)

Morphine dependence is a medical condition characterized by a physical and psychological dependency on morphine, a potent opioid analgesic. This dependence develops as a result of repeated use or abuse of morphine, leading to changes in the brain's reward and pleasure pathways. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) outlines the following criteria for diagnosing opioid dependence, which includes morphine:

A. A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. Opioids are often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowing that a physical or psychological problem is likely to have been caused or exacerbated by opioids.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of opioids to achieve intoxication or desired effect.
b. A markedly diminished effect with continued use of the same amount of an opioid.
11. Withdrawal, as manifested by either of the following:
a. The characteristic opioid withdrawal syndrome.
b. The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms.

Additionally, it's important to note that if someone has been using opioids for an extended period and suddenly stops taking them, they may experience withdrawal symptoms. These can include:

- Anxiety
- Muscle aches
- Insomnia
- Runny nose
- Sweating
- Diarrhea
- Nausea or vomiting
- Abdominal cramping
- Dilated pupils

If you or someone you know is struggling with opioid use, it's essential to seek professional help. There are many resources available, including inpatient and outpatient treatment programs, support groups, and medications that can help manage withdrawal symptoms and cravings.

Morphine is a potent opioid analgesic (pain reliever) derived from the opium poppy. It works by binding to opioid receptors in the brain and spinal cord, blocking the transmission of pain signals and reducing the perception of pain. Morphine is used to treat moderate to severe pain, including pain associated with cancer, myocardial infarction, and other conditions. It can also be used as a sedative and cough suppressant.

Morphine has a high potential for abuse and dependence, and its use should be closely monitored by healthcare professionals. Common side effects of morphine include drowsiness, respiratory depression, constipation, nausea, and vomiting. Overdose can result in respiratory failure, coma, and death.

Naloxone is a medication used to reverse the effects of opioids, both illicit and prescription. It works by blocking the action of opioids on the brain and restoring breathing in cases where opioids have caused depressed respirations. Common brand names for naloxone include Narcan and Evzio.

Naloxone is an opioid antagonist, meaning that it binds to opioid receptors in the body without activating them, effectively blocking the effects of opioids already present at these sites. It has no effect in people who have not taken opioids and does not reverse the effects of other sedatives or substances.

Naloxone can be administered via intranasal, intramuscular, intravenous, or subcutaneous routes. The onset of action varies depending on the route of administration but generally ranges from 1 to 5 minutes when given intravenously and up to 10-15 minutes with other methods.

The duration of naloxone's effects is usually shorter than that of most opioids, so multiple doses or a continuous infusion may be necessary in severe cases to maintain reversal of opioid toxicity. Naloxone has been used successfully in emergency situations to treat opioid overdoses and has saved many lives.

It is important to note that naloxone does not reverse the effects of other substances or address the underlying causes of addiction, so it should be used as part of a comprehensive treatment plan for individuals struggling with opioid use disorders.

Substance Withdrawal Syndrome is a medically recognized condition that occurs when an individual who has been using certain substances, such as alcohol, opioids, or benzodiazepines, suddenly stops or significantly reduces their use. The syndrome is characterized by a specific set of symptoms that can be physical, cognitive, and emotional in nature. These symptoms can vary widely depending on the substance that was being used, the length and intensity of the addiction, and individual factors such as genetics, age, and overall health.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), published by the American Psychiatric Association, provides the following diagnostic criteria for Substance Withdrawal Syndrome:

A. The development of objective evidence of withdrawal, referring to the specific physiological changes associated with the particular substance, or subjective evidence of withdrawal, characterized by the individual's report of symptoms that correspond to the typical withdrawal syndrome for the substance.

B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C. The symptoms are not better explained by co-occurring mental, medical, or other substance use disorders.

D. The withdrawal syndrome is not attributable to another medical condition and is not better accounted for by another mental disorder.

The DSM-5 also specifies that the diagnosis of Substance Withdrawal Syndrome should be substance-specific, meaning that it should specify the particular class of substances (e.g., alcohol, opioids, benzodiazepines) responsible for the withdrawal symptoms. This is important because different substances have distinct withdrawal syndromes and require different approaches to management and treatment.

In general, Substance Withdrawal Syndrome can be a challenging and potentially dangerous condition that requires professional medical supervision and support during the detoxification process. The specific symptoms and their severity will vary depending on the substance involved, but they may include:

* For alcohol: tremors, seizures, hallucinations, agitation, anxiety, nausea, vomiting, and insomnia.
* For opioids: muscle aches, restlessness, lacrimation (tearing), rhinorrhea (runny nose), yawning, perspiration, chills, mydriasis (dilated pupils), piloerection (goosebumps), nausea or vomiting, diarrhea, and abdominal cramps.
* For benzodiazepines: anxiety, irritability, insomnia, restlessness, confusion, hallucinations, seizures, and increased heart rate and blood pressure.

It is essential to consult with a healthcare professional if you or someone you know is experiencing symptoms of Substance Withdrawal Syndrome. They can provide appropriate medical care, support, and referrals for further treatment as needed.

Narcotic antagonists are a class of medications that block the effects of opioids, a type of narcotic pain reliever, by binding to opioid receptors in the brain and blocking the activation of these receptors by opioids. This results in the prevention or reversal of opioid-induced effects such as respiratory depression, sedation, and euphoria. Narcotic antagonists are used for a variety of medical purposes, including the treatment of opioid overdose, the management of opioid dependence, and the prevention of opioid-induced side effects in certain clinical situations. Examples of narcotic antagonists include naloxone, naltrexone, and methylnaltrexone.

Narcotics, in a medical context, are substances that induce sleep, relieve pain, and suppress cough. They are often used for anesthesia during surgical procedures. Narcotics are derived from opium or its synthetic substitutes and include drugs such as morphine, codeine, fentanyl, oxycodone, and hydrocodone. These drugs bind to specific receptors in the brain and spinal cord, reducing the perception of pain and producing a sense of well-being. However, narcotics can also produce physical dependence and addiction, and their long-term use can lead to tolerance, meaning that higher doses are required to achieve the same effect. Narcotics are classified as controlled substances due to their potential for abuse and are subject to strict regulations.

"Matricaria" is a genus of plants in the family Asteraceae, also known as the daisy family. The most common species is Matricaria chamomilla, which is commonly known as chamomile. This plant is native to Europe and Western Asia, and it has been used in traditional medicine for centuries due to its anti-inflammatory, antispasmodic, and calming properties.

The medicinal properties of Matricaria are primarily attributed to its volatile oils, flavonoids, and other chemical constituents found in the flowers and leaves of the plant. Chamomile tea is a popular herbal remedy made from the dried flowers of Matricaria chamomilla, which is often used to promote relaxation, improve sleep quality, and soothe digestive upset.

It's worth noting that while chamomile has been used safely in traditional medicine for many years, it can cause allergic reactions in some people, particularly those with allergies to other members of the Asteraceae family (such as ragweed or daisies). It's always a good idea to consult with a healthcare provider before starting any new herbal remedy.

Drug tolerance is a medical concept that refers to the decreased response to a drug following its repeated use, requiring higher doses to achieve the same effect. This occurs because the body adapts to the presence of the drug, leading to changes in the function or expression of targets that the drug acts upon, such as receptors or enzymes. Tolerance can develop to various types of drugs, including opioids, benzodiazepines, and alcohol, and it is often associated with physical dependence and addiction. It's important to note that tolerance is different from resistance, which refers to the ability of a pathogen to survive or grow in the presence of a drug, such as antibiotics.

Opioid mu receptors, also known as mu-opioid receptors (MORs), are a type of G protein-coupled receptor that binds to opioids, a class of chemicals that include both natural and synthetic painkillers. These receptors are found in the brain, spinal cord, and gastrointestinal tract, and play a key role in mediating the effects of opioid drugs such as morphine, heroin, and oxycodone.

MORs are involved in pain modulation, reward processing, respiratory depression, and physical dependence. Activation of MORs can lead to feelings of euphoria, decreased perception of pain, and slowed breathing. Prolonged activation of these receptors can also result in tolerance, where higher doses of the drug are required to achieve the same effect, and dependence, where withdrawal symptoms occur when the drug is discontinued.

MORs have three main subtypes: MOR-1, MOR-2, and MOR-3, with MOR-1 being the most widely studied and clinically relevant. Selective agonists for MOR-1, such as fentanyl and sufentanil, are commonly used in anesthesia and pain management. However, the abuse potential and risk of overdose associated with these drugs make them a significant public health concern.

Morphine derivatives are substances that are synthesized from or structurally similar to morphine, a natural opiate alkaloid found in the opium poppy. These compounds share many of the same pharmacological properties as morphine and are often used for their analgesic (pain-relieving), sedative, and anxiolytic (anxiety-reducing) effects.

Examples of morphine derivatives include:

1. Hydrocodone: A semi-synthetic opioid that is often combined with acetaminophen for the treatment of moderate to severe pain.
2. Oxycodone: A synthetic opioid that is used for the management of moderate to severe pain, either alone or in combination with other medications.
3. Hydromorphone: A potent semi-synthetic opioid that is used for the treatment of severe pain, typically in a hospital setting.
4. Oxymorphone: A synthetic opioid that is similar to hydromorphone in its potency and use for managing severe pain.
5. Codeine: A naturally occurring opiate alkaloid that is less potent than morphine but still has analgesic, cough suppressant, and antidiarrheal properties. It is often combined with other medications for various therapeutic purposes.
6. Fentanyl: A synthetic opioid that is significantly more potent than morphine and is used for the management of severe pain, typically in a hospital or clinical setting.

It's important to note that while these derivatives can be beneficial for managing pain and other symptoms, they also carry a risk of dependence, addiction, and potentially life-threatening side effects such as respiratory depression. As a result, their use should be closely monitored by healthcare professionals and prescribed cautiously.

'Animal behavior' refers to the actions or responses of animals to various stimuli, including their interactions with the environment and other individuals. It is the study of the actions of animals, whether they are instinctual, learned, or a combination of both. Animal behavior includes communication, mating, foraging, predator avoidance, and social organization, among other things. The scientific study of animal behavior is called ethology. This field seeks to understand the evolutionary basis for behaviors as well as their physiological and psychological mechanisms.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Analgesics, opioid are a class of drugs used for the treatment of pain. They work by binding to specific receptors in the brain and spinal cord, blocking the transmission of pain signals to the brain. Opioids can be synthetic or natural, and include drugs such as morphine, codeine, oxycodone, hydrocodone, hydromorphone, fentanyl, and methadone. They are often used for moderate to severe pain, such as that resulting from injury, surgery, or chronic conditions like cancer. However, opioids can also produce euphoria, physical dependence, and addiction, so they are tightly regulated and carry a risk of misuse.

The brain is the central organ of the nervous system, responsible for receiving and processing sensory information, regulating vital functions, and controlling behavior, movement, and cognition. It is divided into several distinct regions, each with specific functions:

1. Cerebrum: The largest part of the brain, responsible for higher cognitive functions such as thinking, learning, memory, language, and perception. It is divided into two hemispheres, each controlling the opposite side of the body.
2. Cerebellum: Located at the back of the brain, it is responsible for coordinating muscle movements, maintaining balance, and fine-tuning motor skills.
3. Brainstem: Connects the cerebrum and cerebellum to the spinal cord, controlling vital functions such as breathing, heart rate, and blood pressure. It also serves as a relay center for sensory information and motor commands between the brain and the rest of the body.
4. Diencephalon: A region that includes the thalamus (a major sensory relay station) and hypothalamus (regulates hormones, temperature, hunger, thirst, and sleep).
5. Limbic system: A group of structures involved in emotional processing, memory formation, and motivation, including the hippocampus, amygdala, and cingulate gyrus.

The brain is composed of billions of interconnected neurons that communicate through electrical and chemical signals. It is protected by the skull and surrounded by three layers of membranes called meninges, as well as cerebrospinal fluid that provides cushioning and nutrients.

Maintenance of morphine dependence by naloxone in acutely dependent mice.. M Sofuoglu, J Sato and A E Takemori ... Maintenance of morphine dependence by naloxone in acutely dependent mice.. M Sofuoglu, J Sato and A E Takemori ... Maintenance of morphine dependence by naloxone in acutely dependent mice.. M Sofuoglu, J Sato and A E Takemori ... Maintenance of morphine dependence by naloxone in acutely dependent mice. Message Subject (Your Name) has forwarded a page to ...
However, there is no report of the effect of IRAS on morphine tolerance and physical dependence. In the present study, we found ... The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence.. ... The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence. ... The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence. ...
DRUG ABUSE AND DEPENDENCE. Controlled Substance. Morphine Sulfate Injection contains morphine, a Schedule II controlled ... Morphine Sulfate Injection contains morphine, a Schedule II controlled substance. As an opioid, Morphine Sulfate Injection ... MORPHINE SULFATE (UNII: X3P646A2J0) (MORPHINE - UNII:76I7G6D29C) MORPHINE SULFATE. 50 mg in 1 mL. ... MORPHINE SULFATE (UNII: X3P646A2J0) (MORPHINE - UNII:76I7G6D29C) MORPHINE SULFATE. 25 mg in 1 mL. ...
As an opioid, Morphine Sulfate Tablets expose users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ... Conversion from Parenteral Morphine to Morphine Sulfate Tablets For conversion from parenteral morphine to Morphine Sulfate ... Morphine Sulfate Tablets *15 mg: Each tablet contains 15 mg morphine sulfate, USP (equivalent to 11.25 mg morphine) and is a ... Conversion from Morphine Sulfate Tablets to Extended-Release Morphine For a given dose, the same total amount of morphine ...
Morphine Dependence. Morphine -- adverse effects 2. The morphine habit: its causation, treatment, and the possibility of its ... Morphine Dependence. Morphine Dependence -- therapy 3. Breve estudio sobre la morfinomania: trabajo presentado al jurado ... Start Over You searched for: Subjects Morphine Dependence ✖Remove constraint Subjects: Morphine Dependence ... Morphine Dependence. Mentally Ill Persons. Needles. Foreign-Body Migration 5. The morphine habit (morphinomania): with four ...
Morphine. *Oxycodone (Percocet or Oxycontin). These drugs can cause physical dependence. This means that a person needs to take ... Drug abuse and dependence. In: Ritter JM, Flower R, Henderson G, Loke YK, MacEwan D, Rang HP, eds. Rang and Dales Pharmacology ... It is also used as a long-term maintenance medicine for opioid dependence. After a period of maintenance, the dose may be ... Buprenorphine is often combined with Naloxone (Bunavail, Suboxone, Zubsolv), which helps prevent dependence and misuse. ...
Morphine. Immediate release: 10-30 mg every 4-6 h. Controlled release: 15-30 mg every 12-24 h. Constipation, somnolence, ... Risk of addiction, physical dependence, and tolerance. Tramadol. 50-100 mg every 4-6 h (max dose 400 mg daily). Constipation, ... Risk of addiction, physical dependence, and tolerance. Lidocaine. Apply patch to affected area; patch may remain in place up to ... Risk of addiction, physical dependence, and tolerance; avoid use in those with seizures. ...
Ueda H, Ueda M (June 2009). "Mechanisms underlying morphine analgesic tolerance and dependence". Frontiers in Bioscience. 14 ( ... "The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence". Current Opinion in ... Shanazari AA, Aslani Z, Ramshini E, Alaei H (2011). "Acute and chronic effects of morphine on cardiovascular system and the ... Houmes RJ, Voets MA, Verkaaik A, Erdmann W, Lachmann B (April 1992). "Efficacy and safety of tramadol versus morphine for ...
Study: Pure mitragynine "does not induce physiological dependence" in rats, treated morphine withdrawal more efficiently than ... At 3 mg/kg the morphine rats response rate was the same as the control group. However at higher doses the morphine rats ... One group was given morphine, one 98% pure mitragynine, and a control group. Both the morphine rats and MG rats were ... Similarly to the above, the morphine rats response rates plummeted after cessation of the morphine, and took longer to return ...
Substance dependence 05030 Cocaine addiction. 05031 Amphetamine addiction. 05032 Morphine addiction. 05033 Nicotine addiction. ...
But when taken in large amounts over a long period of time, the risk of physical dependence and substance use disorder ... morphine. *hydrocodone. *codeine. Note, though, that addiction is rare when the prescription is taken as prescribed and for ... For people with opioid addiction, opioid withdrawal is one of the most powerful factors driving opioid dependence. Most of what ... which increases the risk of physical dependence and substance use disorder. ...
Categories: Morphine Dependence Image Types: Photo, Illustrations, Video, Color, Black&White, PublicDomain, CopyrightRestricted ...
The present study models this process by using home cage wheel running to assess well-being as a result of pain, morphine ... Opioids such as morphine are the most effective treatment for pain, but termination of opioid use can produce severe withdrawal ... Keywords: Antinociception; Inflammatory pain; Morphine withdrawal; Opioid dependence; Pain-depressed behavior; Wheel running. ... Time course for dark phase wheel running in morphine and placebo treated rats on baseline, morphine, and naloxone treatment ...
He describes his own account of a patient developing a dependence on the drug after he had treated him. By the mid-18th century ... Gibbons discusses opiate addiction resulting from the medical injection of morphine. ...
The use of morphine leads to a metabolic dependence on morphine. Morphine becomes a biologic need just as water and the user ... The morphine addict can not tolerate alcohol when he is using morphine or suffering from morphine withdrawal. The ability to ... Morphine addiction is a metabolic illness brought about by the use of morphine. In my opinion psychological treatment is not ... The patient must have some morphine. If there is one rule that applies to all cases of addiction this is it. But the morphine ...
The use of morphine leads to a metabolic dependence on morphine. Morphine becomes a biologic need just as water and the user ... The morphine addict can not tolerate alcohol when he is using morphine or suffering from morphine withdrawal. The ability to ... Morphine addiction is a metabolic illness brought about by the use of morphine. In my opinion psychological treatment is not ... The patient must have some morphine. If there is one rule that applies to all cases of addiction this is it. But the morphine ...
... operated a maintenance clinic for morphine addicts. The clinic registered 91 patrons by September 1920, when the facility was ... Morphine Dependence / history* Actions. * Search in PubMed * Search in MeSH * Add to Search ... Notes on American medical history: a follow-up study of the New Haven morphine maintenance clinic of 1920 D F Musto, M R Ramos ... Notes on American medical history: a follow-up study of the New Haven morphine maintenance clinic of 1920 D F Musto et al. N ...
1975) Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance. Proc Natl Acad Sci USA 72:3092-3096. ... Chronic morphine treatment was done using time-released morphine pellets (75 mg of morphine per pellet obtained from National ... during acute withdrawal from morphine was studied in slices from animals treated for 6-7 d with morphine. EPSCs were inhibited ... The EC50 for the GABA-B agonist was 2.1 ± 0.8 μm in untreated slices and 0.5 ± 0.3 μm in morphine-withdrawn slices.B, The GABA- ...
The examples are innumerable-from aspirin to morphine to lovastatin. Our dependence today on nature for health has not ... "Our dependence today on nature for health has not diminished as significantly as commonly presumed. Over the past quarter ... Already, species have provided humankind everything from quinine to aspirin, from morphine to numerous cancer and HIV-fighting ... Already, species have provided humankind everything from quinine to aspirin, from morphine to numerous cancer and HIV-fighting ...
Opioids such as oxycodone, morphine, hydrocodone, and fentanyl may be required for individuals with the most severe pain. ... However, opioids can convey heightened pain sensitivity and run the risk of dependence. ...
However, desomorphine showed increased dependence potential compared to morphine. It was briefly marketed in Switzerland in ... Why is Krokodil more addictive than morphine? Its chemical structure renders desomorphine more lipophilic than morphine ... patients with desomorphine dependence inject more frequently than those with heroin dependence. ... Due to the high dependence potential and the toxicity of Krokodil, the mean survival time after first use is reported to be 2 ...
2007) The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence. Curr Opin Neurobiol ... 1984) Opioid receptor reserve in normal and morphine-tolerant guinea pig ileum myenteric plexus. Proc Natl Acad Sci U S A 81: ... 1998) Enhanced opioid efficacy in opioid dependence is caused by an altered signal transduction pathway. J Neurosci 18:10269- ... 2001) Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 81:299-343. pmid:11152760. ...
Spinal matrix metalloproteinase-9 contributes to physical dependence on morphine in mice. J. Neurosci. 30, 7613-7623. doi: ... 2012). Involvement of matrix metalloproteinase-9 in the development of morphine tolerance. Eur. J. Pharmacol. 683, 86-92. doi: ... 2021). Glial IL-33 signaling through an ST2-to-CXCL12 pathway in the spinal cord contributes to morphine-induced hyperalgesia ... 2010). Functional polymorphism of matrix metalloproteinase-9 (MMP-9) gene in alcohol dependence: family and case control study ...
Involvement of Hippocampal Astrocytic Connexin-43 in Morphine dependence.. Darvishmolla M; Heysieattalab S; Saeedi N; ...
09165 Substance dependence. 05032 Morphine addiction. 2564 (GABRE). 05033 Nicotine addiction. 2564 (GABRE). 09180 Brite ...
Schedule II substances have a high potential for abuse, and usage can lead to severe psychological or physical dependence. ... Examples include Dilaudid, hydrocodone, Demerol, OxyContin, Percocet, morphine, fentanyl, codeine, and some amphetamines (ADHD ... Their use has a moderate to low potential for physical or psychological dependence. These drugs include Tylenol with codeine, ...
Drug dependence is now referred to as substance use disorder. Heres what you need to know about this condition. ... A urine test can detect opiates - such as morphine, heroin, and codeine - for up to 3 days after use. Heres what to expect. ... Dependence. Its possible to be dependent on drugs without being addicted. Dependence can be a bodily response to a substance. ... People viewed dependence as a more severe problem than abuse. The APA replaced "dependence" and "abuse" with "substance use ...

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