The role of the nitric oxide (NO) pathway in the discriminative stimuli of amphetamine and cocaine

To examine the role of the nitric oxide (NO) pathway in the stimulus effects induced by some psychostimulants, separate groups of rats were trained to discriminate between amphetamine (AMPH; 0.5 mg/kg) and saline, or cocaine (COC; 5 mg/kg) and saline using a standard two-lever operant procedure. Substitution studies showed that AMPH and COC generalized. for the training drugs in a dose-dependent manner, their ED50 values being 0.1 mg/kg and 1.2 mg/kg, respectively. The dose-response function of both those psychostimulants did not change in the course of the experiment. Moreover, AMPH and COC induced crosssubstitution effects towards each other. Successive combination tests demonstrated that injection of a fixed dose of the NO synthase (NOS) inhibitor 7-nitro indazole (7-NI; 25 mg/kg) plus different doses of AMPH or COC resulted in a leftward shift in the dose-response curves of those psychostimulants and a decrease in their ED50 values. On the other hand, pretreatment with the NO donor molsidomine (MOL), injected in a fixed dose of 100 mg/kg before AMPH and COC, shifted the dose-response curves of the psychostimulants to the right and increased their ED50 values. Our results indicate that NO plays an inhibitory role in the dopamine (DA)-evoked discrimination effects of AMPH and COC in rats. (C) 1998 Elsevier Science Inc.