(+/-)Cyclazocine blocks the dopamine response to nicotine

(+/-)CYCLAZOCINE, synthesized by Archer in 1962, was originally tested as a treatment for heroin addiction. (+/-)Cvclazocine is a mu opioid antagonist and kappa opioid agonist, and because of these actions, would be expected to modulate dopamine release in the nucleus accumbens as well as the reinfo rcing effects of drugs of abuse. In a recent study (+/-)cyclazocine was rep orted to decrease cocaine self-administration in rats. The aim of the prese nt study was to determine whether (+/-)cyclazocine would alter the dopamine rgic effects of nicotine that are thought to mediate its rewarding effects. Using in vivo microdialysis in awake and freely moving rats, we investigat ed the effect of (+/-)cyclazocine (0.5 mg/kg, i.p.) on the acute dopamine r esponse to nicotine (0.32 mg/kg, i.v. over a 5 min period, infused 30 min l ater) in the nucleus accumbens. (+/-)Cyclazocine significantly attenuated t he increase in extracellular dopamine levels induced by the nicotine infusi on and enhanced nicotine-induced increases in dopamine metabolites. (+/-)Cy clazocine alone did not significantly affect extracellular dopamine levels. However, both the (+) and (-) enantiomers of cyclazocine did alter basal d opamine levels and these effects made it difficult to assess their individu al interactions with nicotine. The results suggest that the effects of both enantiomers contribute to the effects of the racemate; (+/-)cyclazocine ma y decrease the rewarding effect of nicotine and may be the prototype of a p otentially novel treatment for smoking. NeuroReport 10:693-696 (C) 1999 Lip pincott Williams & Wilkins.