Effect of acute and chronic treatment with methamphetamine on mRNA expression of synaptotagmin IV and 25 KDa-synaptic-associated protein in the rat brain

The effects of acute and chronic administration of methamphetamine (METH) on mRNA levels of synaptotagmin IV (SytIV) and an isoform of synaptic-associated protein of 25 KDa (SNAP25a) have been investigated in rat brain using in situ hybridization. Pretreatment with 0.5 mg/kg dopamine D1 receptor antagonist (SCH23390), but not 0.5 mg/kg N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801), significantly attenuated the increased SytIV mRNA levels induced by acute METH administration in the striatum and the nucleus accumbens. Pretreatment with 0.5 mg/kg SCH23390, but not 0.5 mg/kg MK-801, significantly attenuated the increased SNAP25a mRNA levels induced by acute METH administration in the striatum and the dentate gyrus of the hippocampus. In the chronic treatment experiment, the SytIV mRNA levels of the group that received chronic treatment with METH followed by a METH challenge showed an increase similar to that seen after acute METH administration. In addition, those in the striatum, nucleus accumbens, and dentate gyrus were significantly higher than those of the group that received chronic treatment with saline followed by a METH challenge. The SNAP25a mRNA levels of the group that received chronic treatment with METH followed by a saline challenge were significantly higher than those of the group that received chronic treatment with saline followed by a saline challenge in the striatum and nucleus accumbens. The results of the present study suggest that SytIV may play an important role in the synaptic plasticity underlying METH-induced neuroadaptive changes including behavioral sensitization.