Antagonism of morphine-induced behavioral suppression by opiate receptor alkylators

Experiments were conducted to test the in vivo opiate specificity and long-lasting effects of two non-equilibrium opiate antagonists: beta-chlornaltrexamine (beta-CNA) and the beta-fumarate methyl ester derivative of naltrexone (beta-FNA). beta-CNA (2.5 or 5.0 micrograms, ICV) partially antagonized suppression of conditioned autoshaped behavior by morphine, when morphine was administered 48-72 hr after beta-CNA. beta-CNA had no effect on amphetamine-induced suppression of autoshaped responding, nor did it antagonize the suppression in rearing activity induced by either morphine or amphetamine. Similarly, beta-FNA (5 mg/kg, IP) antagonized the suppression of conditioned behavior by morphine, for up to 48 hr, while having no effect on amphetamine-induced suppression of autoshaped responding, or on the suppression of rearing activity induced by morphine or amphetamine. Further peripherally administered beta-FNA acts in the brain, since it antagonized analgesia following ICV morphine administration.