The role of benzodiazepine receptors in the acquisition and expression of behavioral sensitization to methamphetamine

The GABA-benzodiazepine neurotransmission has been reported to be implicate d in various forms of plasticity such as kindling and learning. In a previo us study, we have shown that clonazepam (CZP), a GABA-benzodiazepine agonis t, prevents the acquisition of behavioral sensitization to methamphetamine (MA). The present study was conducted to extend this finding by examining t he effect of flumazenil (Flu), a GABA-benzodiazepine antagonist on the prev ention by CZP. Rats (male Wistar-King rats) treated with MA (1 mg/kg, SC) f or 10 days showed significantly enhanced motor activity compared to those t reated with saline when tested with MA (1 mg/kg) after a 7-8-day withdrawal , indicating the acquisition of behavioral sensitization. Representing the previous finding, pretreatment with CZP (0.5 mg/kg) prior to MA administrat ion prevented the acquisition of the phenomenon. Pretreatment with Flu (10 mg/kg) prior to MA administration has no influence on the acquisition of se nsitization. However, pretreatment with Flu prior to CZP administration rev ersed the inhibitory effect of CZP. CZP showed no effect on the expression of sensitization in the sensitized rats when given prior to the MA readmini siration. These results strengthen the suggestion that stimulation of GABA- benzodiazepine receptors plays a role in the acquisition but not in the exp ression of behavioral sensitization to MA. (C) 2000 Elsevier Science Inc.