ENDOGENOUS K-OPIOID SYSTEMS IN OPIATE WITHDRAWAL - ROLE IN AVERSION AND ACCOMPANYING CHANGES IN MESOLIMBIC DOPAMINE RELEASE

The kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) was recently shown to potentiate certain overt withdrawal signs in morphi ne-dependent rats. The present study sought to further assess this phe nomenon by examining the influence of nor-BNI treatment upon the condi tioned place aversion associated with the naloxone-precipitated withdr awal syndrome. In addition, in vivo microdialysis studies were conduct ed in morphine-dependent rats to determine whether nor-BNI treatment c an modify withdrawal-induced changes in basal dopamine (DA) release wi thin the mesolimbic system. Rats were pretreated with either saline or a single dose of nor-BNI and then received ascending doses of morphin e for 10 days. A withdrawal syndrome was then precipitated by the admi nistration of naloxone (1 mg/kg SC). In rats which received chronic mo rphine injections, administration of naloxone produced a characteristi c withdrawal syndrome and a marked aversion for an environment previou sly associated with naloxone-precipitated withdrawal. Nor-BNI treatmen t potentiated most overt signs of physical dependence. This treatment also resulted in a greater withdrawal-induced place aversion. Morphine -dependent rats exhibited a marked reduction in basal mesolimbic DA re lease. An even greater decrease in basal DA release was observed in no r-BNI treated rats. These results suggest that endogenous kappa-system s are important in the modulation of mesolimbic DA release and the acc ompanying place aversion which occurs during opiate withdrawal.