Antagonism of limbic and extrapyramidal actions of intracerebrally injected dopamine by ergolines with partial D2 agonist activity in the rat.
Bromocriptine and a series of experimental ergoline D2 partial agonists (SDZ-208-911, SDZ-212-327, SDZ-208-912) were evaluated for their interactions with exogenous dopamine (DA, at ED50 = 16 micrograms) stereotaxically injected unilaterally into a limbic (superior-medial nucleus accumbens septi) or extrapyramidal (central corpus striatum) target site in rat brain. Behavioral measures to quantify responses were locomotor arousal induced by DA in accumbens and contralateral head turning with striatum. All agents, given systemically (i.p.), induced dose-dependent inhibition of behavioral responses to DA from both brain sites. In both accumbens and striatum, SDZ-212-327 was most potent and bromocriptine, least; however, bromocriptine was relatively much more potent in accumbens, and SDZ-208-912 somewhat more potent in striatum. These results add to the growing impression that agents with partial agonist actions at central DA receptors can show behaviorally inhibitory effects that may reflect paradoxical antidopaminergic actions against the full, natural agonist of DA receptors and that such effects can be regionally selective.
Campbell
A
A
Department of Psychiatry, Harvard Medical School, Belmont, MA.
Baldessarini
R J
RJ
Yeghiayan
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000737:chemistry / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000737:chemistry / Q000494:pharmacology*; D005116:Extrapyramidal Tracts / Q000187:drug effects*; D007267:Injections; D007274:Injections, Intraperitoneal; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D004298:Dopamine