From C.M. Pudiak & M.A. Bozarth (1996). Modification of cocaine self-administration by nitric oxide synthesis inhibition: A potential treatment for cocaine addiction? Society for Neuroscience Abstracts, 22, 703.

MODIFICATION OF COCAINE SELF-ADMINISTRATION BY NITRIC OXIDE SYNTHESIS INHIBITION: A POTENTIAL TREATMENT FOR COCAINE ADDICTION? C.M. Pudiak* & M.A. Bozarth. Addiction Research Unit, Department of Psychology, University at Buffalo, Buffalo, NY 14260.

Studies have shown that animals reliably self-administer stimulants intravenously and that the neurotransmitter dopamine is critically involved in their reinforcing effects. Recently, nitric oxide-containing neurons have been identified in many dopamine-rich brain areas (e.g., striatum, ventral tegmental area), and neurochemical studies have shown that nitric oxide (NO) can modulate stimulant-evoked dopamine release. Results from this laboratory have shown that NO-synthesis inhibition blocks the development of cocaine sensitization and that such inhibition produces a shift in the time course of cocaine's effect on brain stimulation reward without altering cocaine's overall effect.

This study examined the role of NO in mediating cocaine reinforcement. Laboratory rats were tested for intravenous cocaine self-administration 3 hrs/day, 5 days/week with 2 days of no testing intervening between each 5-day block of testing. Once animals showed stable cocaine intake, a 5-day protocol was initiated. Animals self-administered cocaine on all days of testing, and on Day-2 and on Day-5 an intraperitoneal injection of Nw-nitro-L-arginine methyl ester (L-NAME; 3, 30, 300 mg/kg) or saline was administered 45 to 60 minutes into a 3-hr test session. Each injection was separated by a minimum of 72 hrs, and all doses were administered according to a Latin square design.

The results show that L-NAME significantly alters the reinforcement profile of cocaine by decreasing the amount of cocaine self-administered and by increasing the inter-response time between successive cocaine injections. These data suggest that L-NAME prolongs the rewarding effects of cocaine, probably through a pharmacokinetic action. This pharmacokinetic action appears to delay the onset of drug action, to diminish the peak CNS concentration, and to retard elimination from the CNS. Thus, the use of NO inhibitors may prove valuable in the treatment of cocaine addiction by modifying cocaine reinforcement through altered pharmacokinetics.

Supported by Pharmacia and Upjohn (Kalamazoo, MI).

 


© 1997 Addiction Research Unit/University at Buffalo


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