Selective depletion of dopamine in the goldfish pituitary caused by domperidone

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Abstract
The effects of the dopamine type-2 receptor (D-2) antagonist domperidone on pituitary and brain amine concentrations and serum gonadotropin levels in the goldfish were investigated. Domperidone caused a long-lasting, dose-dependent depletion of dopamine in the goldfish pituitary. Pituitary concentrations of 5-hydroxytryptamine (5HT) were unaffected by domperidone treatment. Concentrations of noradenaline, dopamine, and 5HT in the hypothalamus and telencephalon were also unaffected by domperidone treatment. In contrast to the goldfish, dopamine levels in both mouse pituitary and hypothalamus were unaffected by domperidone treatment. The depletion of dopamine was observed in both sexually regressed and recrudescent male and female fish, but elevation of serum gonadotropin levels in response to domperidone treatment occurred only in sexually recrudescent fish. Treatment of sexually recrudescent fish with the D-2 antagonists pimozide, (−)-sulpiride and eticlopride and the dopamine type-1 (D-1) antagonists SKF 83566 and SCH 23390 failed to elicit a depletion of pituitary dopamine or elevation of serum gonadotropin. Treatment of sexually recrudescent fish with domperidone, α-methyl-p-tyrosine or carbidopa elicited comparable depletions of pituitary dopamine and elevations of serum gonadotropin. The results suggest that in addition to D-2 receptor antagonist activity, domperidone has some other neuropharmacological action on dopaminergic neurones in the goldfish pituitary.Key words: domperidone, dopamine, noradrenaline, 5-hydroxytryptamine, pituitary, hypothalamus, telencephalon, gonadotropin, goldfish.

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