Enhanced striatal 3H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase.
Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for 3H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH2 or cyclo(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of 3H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides; D010456:Peptides, Cyclic; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism*; D013997:Time Factors
D002090:Butyrophenones; D004151:Dipeptides; D009479:Neuropeptides; D010456:Peptides, Cyclic; D011954:Receptors, Dopamine; C031611:spiroperidol receptor; D013134:Spiperone; C021166:cyclo(leucylglycine); D009075:MSH Release-Inhibiting Hormone; D006220:Haloperidol; D001058:Apomorphine