Effects of repeated treatment with haloperidol on rat striatal neutral endopeptidase, and on mu- and delta-opioid binding sites: comparison with chronic morphine and chronic kelatorphan.
Neutral endopeptidase (NEP) and mu- and delta-opioid receptor densities were measured in sections of rat striatum by in vitro radioautography with the selective ligands: 3 nM [3H]N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]glycine ([ 3H]HACBO-Gly), 3 nM [3H]Tyr-D.Ala-Gly-(NMe)Phe-Gly-ol ([ 3H]DAGO) and 3 nM [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr ([ 3H]DTLET), respectively. Haloperidol treatment (2 mg/kg/day, i.p., 3 weeks), which has been reported to increase enkephalin levels in the striatum, induced a 23% decrease in striatal (posterior level A= +8.4-8.6 mm) NEP labeling (but no change of mu- and delta-sites). In contrast, no change in NEP occurred after chronic morphine (40-160 mg/kg/day, s.c., 4 days) or kelatorphan (10 nmol/h, i.c.v., 7 days), a mixed inhibitor of enkephalin-degrading peptidases.
Delay-Goyet
P
P
U266 INSERM, UA 498 CNRS, Département de Chimie Organique, Faculté de Pharmacie, Paris, France.
Zajac
J M
JM
Roques
B P
BP
D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004151:Dipeptides / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D015260:Neprilysin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D004151:Dipeptides; D011957:Receptors, Opioid; C042591:kelatorphan; D009020:Morphine; D015260:Neprilysin; D006220:Haloperidol