Role of endogenous enkephalins in locomotion evidenced by acetorphan, an "enkephalinase" inhibitor.
To investigate whether endogenous enkephalins modulate locomotion we studied the effect of the systemic administration of acetorphan, a parenterally active "enkephalinase" inhibitor. Locomotor activity in mice and rats was considered as an index to the activity of mesolimbic dopaminergic neurons. Acetorphan injected i.v. induced an increase in locomotion, mice and rats presenting a similar behavioral response. Naloxone, at low doses, blocked the enhanced motor response. The increased locomotion was antagonized by a pretreatment with haloperidol or potentiated by GBR 12783, a potent and specific inhibitor of dopamine (DA) uptake. The neurotoxic lesion of the mesolimbic DA system with 6-hydroxydopamine abolished the effect of acetorphan. These data suggest that the locomotor hyperactivity induced by the enkephalinase inhibitor results from the protection of local endogenous enkephalins and may be mesolimbic DA-dependent.
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000502:physiology*; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D015244:Thiorphan / Q000031:analogs & derivatives*; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D004745:Enkephalins; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D009270:Naloxone; C049331:racecadotril; D016627:Oxidopamine; D015244:Thiorphan; D008625:Tiopronin; D008666:Metalloendopeptidases; D015260:Neprilysin