Effect of post-trial L-NAME administration on cocaine sensitization.

This study determined if Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) administered after the cocaine-conditioning trial attenuated the development of sensitization to cocaine's locomotor-stimulating effect and secondly, determined if L-NAME blocked conditioned-locomotor activity (LMA) elicited by a saline-challenge injection. Results revealed that cocaine-injected animals (10 mg/kg, i.p.) showed enhanced locomotor activity across the three conditioning trials (all p's < .05). Cocaine-injected animals administered L-NAME (30 mg/kg, i.p.) after each conditioning trial showed a slight increase in cocaine-stimulated LMA from the first to the second conditioning trial (all p's < .05) and no further increases in LMA thereafter. A saline-challenge injection administered 72 hr after the last conditioning trial revealed that cocaine-injected animals displayed as much locomotor stimulation to a saline injection as they did during their initial exposure to cocaine on the first conditioning trial - indicating the development of cocaine-conditioned LMA. The present findings show that L-NAME administered after the cocaine-conditioning trial attenuates the development of sensitization to cocaine's locomotor-stimulating effect. The failure of L-NAME to block cocaine-conditioned LMA suggests that the pharmacological and conditioning mechanisms of sensitization can be dissociated. It is unlikely that L-NAME's effect is due to a sedative action produced by residual L-NAME since animals administered L-NAME (30 mg/kg, i.p.) for 10 consecutive days exhibited a similar responsiveness to a cocaine challenge administered 3 and 10 days following the termination of L-NAME administration. These data support a role for nitric oxide's involvement in the neuroadaptive responses that result from continued stimulant administration and demonstrate the importance of conditioned drug effects.