Expression of microRNAs in methamphetamine-induced rewarding effect

[Speaker] Keisuke Mizuo:1
[Co-author] Satoshi Watanabe:1
1:Department of Legal Medicine, Sapporo Medical University School of Medicine, Japan

Methamphetamine and related psychomotor stimulants produce a strong rewarding and lead to extensive abuse with sociological and psychiatric problems. However, little is known about the mechanisms underlying methamphetamine dependence. Recent studies demonstrated that microRNA (miR) have important role in the regulation of several physiological functions. In the present study, we investigated the expression of miRs in methamphetamine-induced rewarding effect. The rewarding effect was evaluated by conditioned place preference. The pre-conditioning test was performed as follows: the mice that had not been treated with either drugs or saline were then placed in the box. The time spent in each compartment during a 900-sec session was then counted. Conditioning sessions were started on the day after pre-conditioning test and conducted once daily for 6 days. The animals were injected methamphetamine and placed in the compartment opposite that in which they had spent the most time in the pre-conditioning test, for 1 hr. On alternate days, these animals received with vehicle and were placed in the other compartment for 1 hr. On the day after the final conditioning session, a post-conditioning test that was identical to the pre-conditioning test was performed. The mice were killed by decapitation and the limbic forebrain (containing nucleus accumbens) was dissected. RT-PCR analysis for detection of miRs in the brain was performed. We observed that the expression of miR-124 was significantly increased in limbic forebrain of methamphetamine-dependent mice. It has been reported that miR-124 is highly expressed in the brain and plays a critical role in the regulation of synaptic activities. These findings suggest that the increase in the expression of miR-124 may change the synaptic activities, resulting in the development of methamphetamine-induced rewarding effect. We previously reported that the expression of miR-124 was significantly increased in limbic forebrain following chronic treatment of ethanol. It has been reported that miR-124 play a critical role in the dependence of cocaine. Taken together, our findings suggest that the miR-124 is a common miR in the regulation of dependence of abused drugs.
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