Beta-endorphin-(1-27) is a naturally occurring antagonist of the reinforcing effects of opioids

Abstract

A place preference conditioning procedure was used to characterize the motivational effects of beta-endorphin-(1-27), a naturally occurring fragment of beta-endorphin (beta-EP). The intracerebroventricular (ICV) administration of beta-EP, selective mu-(DAGO) or delta-(DPDPE) opioid receptor agonists to rats produced marked preferences for the drug-associated place, whereas the selective kappa-opioid receptor agonist, U-50488H produced conditioned aversions. ICV injections of the beta-EP-(1-27) (5-20 micrograms), however, resulted in no preference for either the drug- or vehicle-associated place. Pretreatment with beta-EP-(1-27) (10 micrograms) eliminated the place preference produced by beta-EP. It abolished the place preferences induced by both DAGO and DPDPE but did not modify the effects of either U-50488H or the psychostimulant d-amphetamine. These data demonstrate that beta-EP-(1-27) selectively antagonizes the motivational effects of mu- and delta-opioid agonists and suggest that this fragment may function as an endogenous antagonist of the reinforcing effects of opioid agonists in vivo.