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: β-chlornaltrexamine (β-CNA) and the β-fumarate methyl ester derivative of naltrexone (β-FNA). β-CNA (2.5 or 5.0 μg, ICV) partially antagonized suppression of conditioned autoshaped behavior by morphine, when morphine was administered 48-72 hr after β-CNA. β-CNA had no effect on amphetamine-induced suppression of autoshaped responding, nor did it antagonized the suppression in rearing activity induced by either morphine or amphetamine. Similarly, β-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 β-FNA acts in the brain, since it antagonized analgesia following ICV morphine administration.