Role of delta opioid receptors in the effects of inhibitors of enkephalin-degrading peptidases on the horizontal and vertical components of locomotion in mice.
In the present study we report the effects of inhibitors of enkephalin-degrading peptidases on spontaneous locomotion in mice and the involvement of delta opioid receptors in these effects. Animals received intracerebroventricularly (i.c.v.) or intravenously (i.v.) enkephalinase inhibitors (thiorphan and acetorphan), aminopeptidase inhibitors (bestatin and carbaphethiol) or mixed peptidase inhibitors (kelatorphan). The i.c.v. co-administration of bestatin and thiorphan (50 micrograms + 50 micrograms) induced an increase in both the horizontal and vertical components of locomotion. A similar pattern was observed after the i.c.v. administration of kelatorphan (8.5-50 micrograms) or the i.v. co-administration of acetorphan and carbaphethiol (5 mg/kg + 10 mg/kg). The opiate antagonist naltrexone (1 mg/kg, s.c.) failed to reverse the excitolocomotor effects of kelatorphan or of bestatin and thiorphan and antagonized only partially the effects of acetorphan and carbaphethiol. Naloxone (2 mg/kg-10 mg/kg, s.c.) partially reversed the increase in locomotion elicited by bestatin and thiorphan. The pretreatment with the delta opioid antagonists ICI 154,129 (20 micrograms, i.c.v.) or ICI 174,864 (2-4 micrograms, i.c.v.) strongly decreased the effects of all the peptidase inhibitors we tested. These results suggest that endogenous enkephalins may control via delta opioid receptors the horizontal and vertical components of locomotor activity in mice.
Michael-Titus
A
A
Unité de Neuropsychopharmacologie Expérimentale, URA 1170 CNRS, U.F.R. de Médecine et Pharmacie, Saint Etienne du Rouvray, France.
Dourmap
N
N
Costentin
J
J
Schwartz
J C
JC
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000818:Animals; D018826:CD13 Antigens; D004151:Dipeptides / Q000494:pharmacology*; D004357:Drug Synergism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D048448:Phenylcarbamates; D011355:Prodrugs / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004151:Dipeptides; D004745:Enkephalins; D048448:Phenylcarbamates; D011355:Prodrugs; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D013438:Sulfhydryl Compounds; C058984:carbaphethiol; D009270:Naloxone; C042591:kelatorphan; D004743:Enkephalin, Leucine; C049331:racecadotril; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; C036405:ICI 154129; D015244:Thiorphan; D000626:Aminopeptidases; D018826:CD13 Antigens; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex