Beta-endorphin-(1-27) is a naturally occurring antagonist of the reinforcing effects of opioids.
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.
Bals-Kubik
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Department of Neuropharmacology, Max-Planck-Institut für Psyhiatrie, Planegg-Martinsried, Federal Republic of Germany.
Herz
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Shippenberg
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D000818:Animals; D006328:Cardiac Catheterization; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D007276:Injections, Intraventricular; D008297:Male; D009042:Motivation / Q000187:drug effects; D009292:Narcotic Antagonists; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D009292:Narcotic Antagonists; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; C035581:beta-endorphin (1-27); D003913:Dextroamphetamine