Actin Dynamics in Development of Behavioral Sensitization After Withdrawal from Long-Term Ethanol Administration to Mice

Authors


Reprint requests: Seitaro Ohkuma, MD, PhD, Professor, Department of Pharmacology, Kawasaki Medical School, Matsushima, Kurashiki 701-0192, Japan; Tel.: +81-86-462-1111; Fax: +81-86-462-1199; E-mail: sohkuma@bcc.kawasaki-m.ac.jp

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.

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