Dopamine receptors: effects of chronic L-dopa and bromocriptine treatment in an animal model of Parkinson's disease.
Male albino rats received a stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra. Animals demonstrating contralateral rotations 2 weeks postoperatively with apomorphine (0.5 mg/kg i.p.) were treated with L-Dopa (55 mg/kg i.p.), bromocriptine (2 mg/kg i.p.), or polyethylene glycol (vehicle) every 12 h for 30 days. Striatal dopamine (DA) receptors were analyzed by Scatchard plot using 3H-spiroperidol (3H-SP) as ligand. 3,4-Dihydroxyphenylacetic acid (DOPAC) and DA were measured by use of high pressure liquid chromatography. 6-OHDA lesions produced a supersensitivity in striatal DA receptors. Chronic L-Dopa or bromocriptine treatment reversed this supersensitivity. Neither lesion nor drug treatment alone or together produced a significant change in affinity (KD) for 3H-SP. Drug treatment alone also had no effect on Bmax. DA and DOPAC levels were reduced by greater than 98% in lesioned striata. Neither drug treatment affected DA or DOPAC levels as compared with controls. These results indicate that chronic administration of either bromocriptine or L-Dopa will reverse the DA receptor denervation supersensitivity in striatum seen following 6-OHDA lesion. This reversal may play a role in the clinical changes seen in Parkinson's disease patients following chronic use of these drugs.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008566:Membranes / Q000378:metabolism; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D001971:Bromocriptine; D007980:Levodopa; D013134:Spiperone; D016627:Oxidopamine; D004298:Dopamine