aconitine and Alcoholism

The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs). Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, alpha-conotoxin MII (alphaCtxMII, alpha(3)beta(2)*, beta(3)*, alpha(6)*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-beta-erythroidine (DHbetaE, alpha(4)beta(2)*), and methyllycaconitine (MLA, alpha(7)*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats.. The effects of drugs were studied in rats trained for operant oral self-administration of ethanol (FR = 1). For ethanol deprivation, trained animals were subjected to a period of alcohol deprivation for 10 days. alphaCtxMII was given directly into the VTA through implanted permanent intracranial cannulae, whereas MEC, DHbetaE, and MLA were administered systemically.. alphaCtxMII reduced operant ethanol self-administration and blocked the deprivation-induced relapse-like ethanol consumption. MEC reduced operant ethanol self-administration and inhibited the deprivation-induced increase in alcohol consumption. DHbetaE did not alter ethanol self-administration in the lower-dose range but inhibited ethanol intake at a higher dose (4 mg/kg), although this effect might have been nonspecific. MLA failed to block self-administration of ethanol and relapse-like drinking after deprivation.. Our results indicate that nAChRs are involved in the modulation of operant alcohol self-administration and relapse-like alcohol drinking behavior in rats. Our observations support the working hypothesis that systemically active selective ligands for nAChR alpha(3)beta(2)*, beta(3), and/or alpha(6)* receptor subunits might be of therapeutic value for the treatment of alcoholism.

Topics: Aconitine; Administration, Oral; Alcohol Drinking; Alcoholism; Animals; Behavior, Animal; Central Nervous System Agents; Conditioning, Operant; Conotoxins; Dihydro-beta-Erythroidine; Dose-Response Relationship, Drug; Ethanol; Male; Mecamylamine; Nicotinic Antagonists; Protein Subunits; Rats; Rats, Wistar; Receptors, Nicotinic; Recurrence; Self Administration; Ventral Tegmental Area

A number of studies have reported that ethanol exposure induces changes in different brain systems. The hippocampus is a brain region that is very vulnerable to ethanol exposition, which functionally results in impairment of learning and memory processes reported in heavy drinkers. Hippocampal nicotinic receptors are involved in learning and memory. In this study, we determined the effects of ethanol on the main hippocampal subtypes of neural nicotinic receptors (alpha7 and alpha4beta2) in rats non-selected for alcohol consumption, in order to check for possible changes on these receptors that could be linked with alterations in learning acquisition. Binding assays were carried out with [3H]methyllycaconitine ([3H]MLA) to study the alpha7 and [3H]nicotine to study alpha4beta2 receptors. Auto-shaping, continuous ratio and extinction procedures were used as behavioral tests. The results show that moderate chronic ethanol consumption for 10 weeks produces: (a) a decrease of both hippocampal nicotinic receptor subtypes without alterations in affinity; (b) no differences in behavioral performance between control rats and ethanol-drinking rats in auto-shaping and continuous ratio; (c) an improvement of performance of extinction paradigm. These results indicate that chronic ethanol consumption, at moderate levels, induces changes in hippocampal nicotinic receptors but does not impair acquisition and performance of new associative learning and even improves some kind of paradigms. These results may have implications in the biochemical basis of interactions between alcohol and nicotine and the effects of these drugs on behavior.

Topics: Aconitine; Alcoholism; Animals; Association Learning; Central Nervous System Depressants; Ethanol; Hippocampus; Male; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Rats; Rats, Wistar; Receptors, Nicotinic; Tritium