Effect of dopaminergic and alpha-adrenergic modulation on corticotropin-releasing factor immunoreactivity in rat hypothalamus.
The potential role that dopaminergic mechanisms have in the regulation of corticotropin-releasing factor (CRF) in the hypothalamus was investigated. Adult male rats were administered bromocriptine, a potent dopamine agonist, for periods ranging up to 51 days. Overall, bromocriptine treatment resulted in a significant decline in CRF-like immunoreactivity (CRF-ir). The dopamine antagonist, haloperidol, was administered for similar periods and resulted in no overall significant effect, except for a transient decrease. Treatment with reserpine, known to deplete monoamines including dopamine, induced a significant decrease in CRF-ir 24 h post-treatment. The possibility that the original results were due to alpha-adrenergic inhibition by bromocriptine and haloperidol was studied next. alpha 1-Stimulation by administration of methoxamine had no significant effect. alpha 2-Stimulation by clonidine significantly reduced hypothalamic CRF-ir. Selective depletion of neurotransmitter from noradrenergic and adrenergic neurons by 6-hydroxydopamine also resulted in a significant reduction of hypothalamic CRF-ir, an effect localized entirely to the median eminence. These results show a reduction in CRF-ir subsequent to either bromocriptine administration, generalized monoamine depletion, alpha 2-stimulation, or selective noradrenaline-adrenaline depletion. No direct dopaminergic effects could be confirmed. These data are consistent with a constant, near-maximal alpha 1-adrenergic effect maintaining hypothalamic CRF concentrations, presumably by inhibition of CRF release from the median eminence.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000032:analysis*; D015259:Dopamine Agents / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D015259:Dopamine Agents; D006892:Hydroxydopamines; D001971:Bromocriptine; D012110:Reserpine; D016627:Oxidopamine; D003346:Corticotropin-Releasing Hormone; D008729:Methoxamine; D006220:Haloperidol; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine