Hypothesis: bromocriptine lacks intrinsic dopamine receptor stimulating properties.
Bromocriptine (BRC) produced neither locomotor stimulation nor stereotyped behavior in mice and rats pretreated with reserpine plus alpha-methyl-p-tyrosine (AMPT). However, the blockade of locomotor stimulation in mice by AMPT could be reversed by their prior treatment with a low, behaviorally inactive dose of L-DOPA. BRC potentiated the stereotypy (rats) and locomotor stimulation (mice) produced by apomorphine in animals pretreated with reserpine plus AMPT. Moreover, BRC potentiated the stimulant effect of d-amphetamine in reserpinized mice, while nomifensine, but not fluoxetine or desipramine, potentiated the stimulant effect of BRC in mice. After direct application to the nucleus accumbens or caudate nucleus of rats, BRC was inactive. However, when BRC and DA were applied together to the nucleus accumbens, BRC enhanced the stimulant effect of DA. These data show that BRC by itself does not cause behavioral stimulation in rodents. Despite having affinity for the DAD 2-receptor, BRC is incapable of causing excitation in rats and mice unless another DA-receptor agonist such as apomorphine or DA is present. The data are discussed in relation to the published literature and the hypothesis presented that BRC affects the signal transmitted by DA-receptor agonists such as apomorphine at or beyond the postsynaptic DA-receptor.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009526:Nialamide / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D011954:Receptors, Dopamine; D005473:Fluoxetine; D009627:Nomifensine; D001971:Bromocriptine; D019805:alpha-Methyltyrosine; D012110:Reserpine; D000262:Adenylyl Cyclases; D009526:Nialamide; D003891:Desipramine; D003913:Dextroamphetamine