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Alcohol Clin Exp Res. 2012 Aug;36(8):1385-96. doi: 10.1111/j.1530-0277.2012.01747.x. Epub 2012 Feb 29.

Actin dynamics in development of behavioral sensitization after withdrawal from long-term ethanol administration to mice.

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  • 1Department of Pharmacology, Kawasaki Medical School, Kurashiki, Japan.

Abstract

BACKGROUND AND METHODS:

The present study investigated the role of actin depolymerizing factor (ADF) in the brain of mice after withdrawal from continuous ethanol (EtOH) vapor inhalation for 9 days using C57BL/6J and ADF mutant mice.

RESULTS:

C57BL/6J mice with withdrawal signs 10 hours after withdrawal from EtOH vapor inhalation showed transient and significant enhancement of locomotor activity by a single injection of EtOH (2 g/kg, i.p.) and of EtOH-induced place preference 3 days after withdrawal from EtOH vapor inhalation, suggesting the development of sensitization of locomotion activity to EtOH and of place preference 3 days after withdrawal from EtOH in C57BL/6J mice with EtOH physical dependence. The levels of ADF and G-actin in the ventral tegmental area, including a little bit of surrounding tissues, increased immediately (0 hours), 10 hours, and 3 days after withdrawal from EtOH vapor. F-actin, synaptic vesicle-associated protein 38, and postsynaptic density 95 increased 0 hours and 3 days after withdrawal with their decreases 10 hours after withdrawal from EtOH vapor. An F-actin stabilizing agent phalloidin (3 nmol/mouse/d, i.c.v., once a day) administered daily for 3 days after withdrawal from continuous EtOH vapor inhalation for 9 days significantly suppressed the increase in both EtOH-induced place preference and locomotor activity by a single injection of EtOH 3 days after withdrawal from long-term EtOH vapor inhalation for 9 days. In addition, the changes in behavioral sensitization in ADF mutant mice were significantly weaker than those observed in C57BL/6J mice (wild-type mice for ADF mutant mice).

CONCLUSIONS:

The findings presented here suggest that withdrawal from EtOH physical dependence causes behavioral sensitization to EtOH, which may be, at least in part, mediated by alternation of actin dynamics.

Copyright © 2012 by the Research Society on Alcoholism.

[PubMed - indexed for MEDLINE]
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