title: Effect of post-trial L-NAME administration on cocaine sensitization.
abstract: 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.
authors.affiliation: Addiction Research Unit, Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA. C.Pudiak@yahoo.com
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Pudiak
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bozarth
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D003042:Cocaine; D019331:NG-Nitroarginine Methyl Ester