Role of nitric oxide in amphetamine-induced sensitization of schedule-induced polydipsic rats

Rationale Repeated injections of amphetamine (AMPH) can progressively augment behavioral responses, a phenomenon known as behavioral sensitization. AMPH-induced behavioral sensitization can be demonstrated in a rat model of schedule-induced polydipsia (SIP). Objectives The aim of this study was to investigate the effects of a nonspecific nitric oxide (NO) synthase inhibitor, N(G)-nitro arginine methyl ester (l-NAME), on the AMPH sensitization effects in SIP. Materials and methods Rats were trained to establish SIP. The induction of AMPH sensitization in SIP was tested in either the home cage or a test cage. l-NAME (50 mg/kg, i.p.) was co-administered with AMPH for five consecutive days, and its effect on induction was examined 3 and 14 days after withdrawal. The effect of l-NAME on expression was examined on the final testing day by co-administration with AMPH in previously sensitized SIP rats. Results AMPH-induced behavioral sensitization in SIP rats only occurred when AMPH was injected in the home cage. Pretreatment with l-NAME successfully blocked the induction of this sensitization following both short and long-term withdrawal. Once sensitization had been established, l-NAME had no further influence. Conclusions These results suggest that SIP behavior observed after repeated AMPH treatment is mediated by an NO-associated mechanism.