Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this review is to summarize the effects of acute and chronic treatment with barbiturates, ethanol and benzodiazepines on cholinergic mechanisms in the brains of experimental animals. A single dose of each of these substances reduces the turnover of ACh in the brain. Long-term treatment has the opposite effect; complicated interactions including decreased content of ACh are induced. Barbiturates have been shown to bind stereospecifically to muscarinic and nicotinic receptors in the brain, but this has not been observed for ethanol or the benzodiazepines. The effects on the cholinergic system are affected by the length of treatment and choice of treatment regimen. No effect on cholinergic parameters, such as muscarinic receptors, in the brain is observed on withdrawal of ethanol or barbiturate treatment when the animals are still tolerant towards the substances. The increase in the number of muscarinic receptors observed in several brain regions on withdrawal is seen as a sign of cholinergic supersensitivity. The number of receptors returns to normal when abstinence convulsions have occurred. The assumption of a cholinergic influence is supported by the finding that atropine, given as a single dose on the day of withdrawal of barbital, can prevent the muscarinic receptor changes. Furthermore, long-term barbital or ethanol treatment can induce permanent persistent changes in the cholinergic system in the brain. Cognitive defects and a significant permanent reduction in the content of ACh can be measured in rats which have had long-term barbital treatment. Similarly, a reduced number of muscarinic receptors has been measured in different brain regions of chronic alcoholics. Accumulating data support the role of the cholinergic system in expressing symptoms of physical dependence on barbiturates, ethanol and benzodiazepines as well as in the permanent long-term effects observed after end of treatment.
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PMID:Cholinergic mechanisms in physical dependence on barbiturates, ethanol and benzodiazepines. 135 20

In the hippocampus of human alcoholics, prolonged ethanol treatment reduces the number of muscarinic ligand binding sites present at autopsy suggesting a decrease in functional muscarinic receptors. Whether these changes are due to alcohol-induced brain damage or ethanol dependence and represent a reduced level of cholinergic function is unknown. The present studies tested the impact of ethanol dependence or long-term ethanol treatment and subsequent withdrawal on the function of pre- and postsynaptic muscarinic receptors in the CA1 region of the rat hippocampus. Field excitatory postsynaptic potentials (EPSPs) were inhibited in a concentration-dependent manner by 0.1-100 microM carbachol. This presynaptic inhibitory action of carbachol involving muscarinic receptors was not significantly reduced either by ethanol treatment (12 days), causing physical dependence, or by long-term ethanol treatment (97-120 days) and abstinence (3-6 months). Postspike after hyperpolarizations (AHPs) were inhibited in a concentration-dependent manner by carbachol (6-2000 nM). This postsynaptic excitatory action of muscarinic receptors also was not significantly reduced either by 12-day ethanol treatment or by long-term ethanol treatment. Taken together, these results suggest that neither pre- nor postsynaptic muscarinic receptor function measured electrophysiologically is reduced by either ethanol dependence or long-term ethanol consumption and abstinence in the rat as suggested by reduced muscarinic ligand binding in the hippocampus of human alcoholics.
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PMID:Acute ethanol dependence or long-term ethanol treatment and abstinence do not reduce hippocampal responses to carbachol. 774 11

Treatment of opiate addiction is generally directed at the suppression of withdrawal symptoms through maintenance of the 'addicted' state with methadone. Yet relatively little is known regarding the neural substrates that contribute to, and maintain the prolonged state of withdrawal experienced by addicts. Opiates can profoundly alter the dynamics of brain and peripheral cholinergic systems, and central administration of anticholinergic drugs in dependent rats has been shown to decrease the expression of precipitated withdrawal symptoms. The purpose of this study was to determine whether the adaptive changes to M2 muscarinic receptors in autonomic centers are linked to the expression of withdrawal phenomena. During the peak period of withdrawal, there was a significant increase in both the expression of M2 muscarinic receptors and its corresponding mRNA within the rostral ventrolateral medulla, a primary vasomotor region. That most of these changes in receptor expression were adaptive in nature was suggested by the fact that when the acetylcholinesterase inhibitor DFP was co-administered with morphine, both the increased mRNA expression and the appearance of withdrawal symptoms were inhibited. Thus, interference with morphine-induced M2 muscarinic receptor adaptation in critical brain regions was correlated with a reduction in the development of physical dependence.
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PMID:Prevention of morphine-induced muscarinic (M2) receptor adaptation suppresses the expression of withdrawal symptoms. 972 19