THE EFFECTS OF THE KAPPA-AGONIST U-50,488 ON COCAINE-INDUCED CONDITIONED AND UNCONDITIONED BEHAVIORS AND FOS IMMUNOREACTIVITY

The ability of kappa opioid agonists to modulate dopamine-mediated beh avior and Fos immunoreactivity was assessed in adult rats. It was pred icted that kappa agonist treatment would block the unconditioned and c onditioned behaviors produced by cocaine (an indirect dopamine agonist ). In the initial experiments, cocaine-induced locomotor activity was assessed after either acute or chronic injections of the kappa recepto r agonist U-50,488 (5 mg/kg, SC). As expected, U-50,488 decreased coca ine-induced activity, while leaving baseline activity levels unaffecte d. Interestingly, chronic treatment with U-50,488 did not induce behav ioral tolerance. The conditioned effects of cocaine (20 mg/kg, IF) wer e assessed using the conditioned place preference (CPP) paradigm. As e xpected, rats showed a preference for the cocaine-paired compartment, an effect blocked by U-50,488 (5 mg/kg, SC). One hour after CPP testin g, rats were killed and Fos immunoreactivity was assessed. Rats condit ioned with cocaine, but not U-50,488, showed increased Fos activity in the anterior cingulate cortex, piriform cortex, lateral septal area, and olfactory tubercles. When considered together, these results sugge st that U-50,488 was effective at blocking the unconditioned and condi tioned effects of cocaine, as well as cocaine-induced neuronal activit y (as measured by Fos induction).