title: [Mechanism of withdrawal syndrome in alcohol dependence].
abstract: Pathophysiological process of ethanol physical dependence and its withdrawal syndrome is supposed to result from adaptive changes in a number of neurotransmission systems, and several reports have demonstrated functional relationship between behavioral responses and neurotransmission systems in ethanol-dependent and -withdrawn animals. However, the molecular mechanisms underlying behavioral responses observed in these animals are still controversial at present. Alterations of beta-adrenergic receptor (beta-AR) function in the brains of mice physically dependent on ethanol were examined because of few available data on functional changes of beta-ARs and its significance in ethanol withdrawal signs. The protein level of beta-ARs also significantly increased in the frontal cortex of mouse with ethanol physical dependence and conditions withdrawn from ethanol after chronic treatment with ethanol vapor for 9 days. Intracerebroventricular administration of nadolol, a non-selective antagonist for beta-ARs, immediately after discontinuation of ethanol inhalation clearly attenuated the expression of withdrawal signs. These findings suggests that ethanol physical dependence induces beta-AR up-regulation, that is their increased number and facilitation of beta-AR signaling, which may at least in part participates in expression of tonic-clonic convulsion as one of ethanol withdrawal signs. We further investigated relationship between actin of cytoskeleton and relapse of alcohol dependence after withdrawal from alcohol vapor inhalation for 9 days. After 3 days of withdrawal from alcohol vapor alcohol-induced place preference was enhanced, which was blocked by the treatment with an actin polymerization inhibitor, cytochalasin D, and anactin depolymerization inhibitor, phalloidin, during 3 days after ethanol withdrawal. These findings suggest that changes in actin turnover on withdrawal from alcohol vapor involve in sensitization of alcohol-induced place preference.
authors.affiliation: Department of Pharmacology, Kawasaki Medical School, Matsushima 577, Kurashiki 701-0192, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuno
authors.forename: Seitaro
authors.initials: S
authors.lastname: Ohkuma
mesh_terms: D000199:Actins / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology / Q000627:therapeutic use; D004837:Epinephrine / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D010590:Phalloidine / Q000494:pharmacology / Q000627:therapeutic use; D058105:Polymerization / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D009435:Synaptic Transmission; D015854:Up-Regulation
chemical_list: D000199:Actins; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D010590:Phalloidine; D015638:Cytochalasin D; D000431:Ethanol; D004837:Epinephrine