GABAPENTIN BLOCKS METHAMPHETAMINE-INDUCED SENSITIZATION AND CONDITIONED PLACE PREFERENCE VIA INHIBITION OF α2/δ-1 SUBUNITS OF THE VOLTAGE-GATED CALCIUM CHANNELS

Our previous investigation demonstrated that repeated administration of morphine significantly enhanced alpha(2)/delta-1 subunit expression in the frontal cortex and limbic forebrain of mice as well as morphine-induced place preference. However, little is known about regulatory mechanisms of alpha(2)/delta-1 subunit expression in conditioned place preference by methamphetamine (METH). In the present study, we investigated the role of alpha(2)/delta-1 subunit of voltage-gated calcium channels (VGCCs) in the mouse brain under repeated treatment with METH. The level of alpha(2)/delta-1 subunit increased significantly in the limbic forebrain including the nucleus accumbens and the frontal cortex of mice showing METH-induced sensitization. Under these conditions, the development of behavioral sensitization induced by the intermittent administration of METH was significantly suppressed by the co-administration of gabapentin (GBP) with binding activity to an exofacial epitope of alpha(2)/delta-1 subunit. Furthermore, GBP administered i.c.v. caused a dose-dependent inhibition of the METH-induced place preference. Chronic GBP treatment at the dose alleviating sensitization and place preference significantly reduced the elevation of alpha(2)/delta-1 subunit of VGCC induced by the repeated administration of METH in the limbic forebrain and frontal cortex, whereas there were no changes in the increase of alpha(2)/delta-1 subunit mRNA. These findings indicate that alpha(2)/delta-1 subunit plays a critical role in the development of METH-induced place preference following neuronal plasticity, and that GBP, which significantly suppressed METH-induced place preference by its possible inhibitory action of alpha(2)/delta subunit to neuronal membrane, may possibly be used as an alternative drug to treat or prevent drug dependence. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.