Effects of cyclo (Leu-Gly) on neurochemical indices of striatal dopaminergic supersensitivity induced by prolonged haloperidol treatment.
The effects of a prolonged treatment with cyclo (Leu-Gly) and/or haloperidol on biochemical parameters indicative of striatal dopamine target cell supersensitivity have been investigated in the rat. When given acutely, cyclo (Leu-Gly) (2 mg/kg sc) did not affect striatal homovanillic acid, dihydroxyphenylacetic acid and acetylcholine levels both under basal conditions or after acute haloperidol (1 mg/kg ip) treatment. When given concomitantly with haloperidol (infused by means of osmotic minipumps at a rate of 2.5 micrograms/h sc) for 14 days, cyclo (Leu-Gly)(2 mg/kg sc once daily) failed to prevent the fall of striatal dopamine metabolites observed 2 days following withdrawal and the tolerance to the elevation of dopamine metabolites which occurs in response to challenge with the neuroleptic during withdrawal. Prolonged treatment with cyclo (Leu-Gly) also failed to affect the tolerance to the decrease of striatal acetylcholine levels which occurs under chronic haloperidol treatment. These data suggest that the mechanism whereby cyclo (Leu-Gly) inhibits the development of neuroleptic-induced dopaminergic supersensitivity does not involve an action of the peptide on nigro-striatal dopaminergic and striatal cholinergic neurons and is probably exerted distally to both dopaminergic and cholinergic synapses.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009479:Neuropeptides; D010456:Peptides, Cyclic; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D004151:Dipeptides; D009479:Neuropeptides; D010456:Peptides, Cyclic; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; C021166:cyclo(leucylglycine); D006220:Haloperidol; D000109:Acetylcholine; D004298:Dopamine; D006719:Homovanillic Acid