NALOXONE INHIBITS THE REINFORCING AND MOTIVATIONAL ASPECTS OF COCAINEADDICTION IN MICE

The opioid receptor antagonist naloxone is known to influence a wide r ange of behavioral effects of cocaine, including its addictive propert y. In the present study the effects of different doses of naloxone and naloxone-methyl-iodide, a methylated analogon of naloxone that does n ot penetrate the blood-brain barrier, on the action of cocaine in the intravenous self-administration and conditioned place preference (CCP) paradigm were assessed. Systemic naloxone, but not naloxone-methyl-io dide, dose-dependently suppressed cocaine intake during self-administr ation and decreased the preference for the cocaine-associated compartm ent in the CCP paradigm. A significant blockade of cocaine's effects w as only present at a relatively high dose of NLX (1.0 mg/kg, s.c.). In addition, NLX produced a rightward shift in the inverted U-shaped dos e-response curve for cocaine reward during self-administration, indica ting a decrease in sensitivity for the reinforcing effects of cocaine. These data demonstrate that blockade of opioid receptors in the brain block both the reinforcing and conditioned motivational effects of co caine. An interaction between endogenous opioid systems and local dopa minergic systems is suggested in mediating the effects of NLX on cocai ne.