Central dopamine receptors mediating pergolide-induced elevation of serum corticosterone in rats. Characterization by the use of antagonists.
Fourteen dopamine antagonists were compared for their ability to antagonize the elevation of the concentration of serum corticosterone in rats by pergolide, a dopamine agonist. Clozapine did not antagonize the effect of pergolide at the largest dose (10 mg/kg) that could be tested without alteration of basal levels of corticosterone. For the other antagonists, calculation of ED50 values [dose antagonizing by 50% the elevation of corticosterone caused by a 0.3 mg/kg (i.p.) dose of pergolide mesylate] revealed the following order of potency: spiperone greater than loxapine greater than fluphenazine greater than perphenazine greater than flupentixol greater than haloperidol greater than cyclophenazine greater than zotepine greater than flumezapine greater than molindone greater than metoclopramide greater than chlorpromazine greater than sulpiride. All of these compounds caused increases in the concentration of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the brains of rats. The dose that increased the concentration of DOPAC to 200% of the control value (ED200) was calculated for each compound. The ratio of the ED50 value for antagonism of the elevation of corticosterone induced by pergolide to the ED200 value for the elevation of DOPAC in brain varied, probably related to differing selectivity for pre- versus postsynaptic dopamine receptors between the compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D010479:Pergolide; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D010479:Pergolide; D003345:Corticosterone; D006719:Homovanillic Acid