EFFECTS OF CYCLAZOCINE ON COCAINE SELF-ADMINISTRATION IN RATS

Cyclazocine is a K-opioid receptor agonist and CL-opioid receptor anta gonist that was studied in the 1960s as a potential treatment for hero in addicts. Based on the evidence that opioid mechanisms modulate the reinforcing effects of cocaine, it has been suggested that cyclazocine be reconsidered for use in treating cocaine dependence. In the presen t study, the effects of orally administered(+/-)-cyclazocine, (+)-cycl azocine and (-)-cyclazocine on intravenous cocaine self-administration were assessed in rats. (+/-)-Cyclazocine produced a dose-related (2-8 mg/kg) decrease in cocaine intake without affecting bar-press respond ing for water. Neither enantiomer significantly altered responding for either cocaine or water. The efficacy of orally administered (+/-)-cy clazocine on cocaine self-administration was comparable to that previo usly observed using the intraperitoneal route. Distinct actions of the enantiomers of cyclazocine that might contribute to the unique effica cy of the racemate are discussed. Although the mechanistic basis for t he results are not entirely understood, the data suggest that (+/-)-cy clazocine should be considered as a potential treatment for cocaine de pendence. (C) 1998 Elsevier Science B.V. All rights reserved.