INVOLVEMENT OF MESOLIMBIC KAPPA-OPIOID SYSTEMS IN THE DISCRIMINATIVE STIMULUS EFFECTS OF MORPHINE

The neuroanatomical basis of opiate addiction has been studied using a variety of behavioural techniques. The aim of the present study was t o investigate the role of mesolimbic opioid systems, in particular kap pa-opioid systems, in the expression of the discriminative stimulus ef fects of abused drugs. Rats were trained to discriminate morphine (3.0 mg/kg s.c.) from saline under a fixed ratio schedule of food reinforc ement. Once rats had acquired the discrimination, a randomized sequenc e of different doses of the highly selective kappa-opioid receptor ago nist U69593 (0.02-0.16 mg/kg s.c.) was given 20 min prior to a systemi c morphine injection. U69593 dose-dependently blocked the morphine dis crimination. It is important to note that U69593 at these doses failed to generalize to the systemic morphine cue. The site of action by U69 593 (0.02-0.16 mu g) was examined by microinjecting discrete amounts i nto target brain regions. Intra-nucleus accumbens injections of U69593 dose-dependently blocked the systemic morphine cue, whereas, U69593 f ailed to generalize to the discriminative stimulus. The same doses did not affect morphine discrimination after intra-ventral tegmental area or striatum injections. Besides the rewarding effects of drugs of abu se, the discriminative stimulus properties of these agents are seen as a major factor in drug seeking behaviours. The present study shows th at the discriminative effects of morphine, a measure of the subjective effects of this drug can be blocked by the activation of kappa-opioid receptors located in the nucleus accumbens. In view of these findings which show that the activity of endogenous kappa-opioid systems (dyno rphin) may serve as physiological antagonists to counteract the effect s of morphine, kappa-agonists therefore may be useful in the treatment of opioid addictions.