Stimulation of prolactin secretion by neuroleptics in rats with medial basal hypothalamic lesions.
The ability of dopamine receptor antagonists to stimulate prolactin release in rats with medial basal hypothalamic lesions was investigated. Starting levels of prolactin were elevated to approximately 400 ng/ml in animals in which the tuberoinfundibular dopaminergic neurons were completely destroyed by the lesion. In lesioned animals, chlorpromazine administration at doses of 0.1 and 5 mg/kg induced a further 2- to 3-fold significant increase in plasma prolactin levels. the incubation of anterior pituitaries from lesioned animals with 10(6) M chlorpromazine had no effect on prolactin secretion, thereby eliminating the possibility that chlorpromazine itself stimulates prolactin release from the anterior pituitary. A similar increase in plasma prolactin in lesioned rats was also observed with the potent dopamine antagonist d-butaclamol (1 mg/kg). The effect was stereospecific since the inactive isomer l-butaclamol did not produce any change in the circulating levels of prolactin. Pimozide, another dopaminergic antagonist, was ineffective in inducing a further increase in prolactin in lesioned rats when 0.63 mg/kg was used. However, at a 10-fold lower concentration (0.63 mg/kg), pimozide stimulated a significant increase in prolactin in lesioned rats. The involvement of an alpha-adrenergic mechanism was ruled out by the inability of phentolamine (2.5 mg/kg) to increase prolactin secretion. These data suggest that dopaminergic antagonists can further increase prolactin levels in medial basal hypothalamus-lesioned rats possibly by blocking the inhibitory action of dopamine from nonhypothalamic sources, or by releasing a substance which possesses prolactin-releasing activity.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002069:Butaclamol / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D007033:Hypothalamus, Middle / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011388:Prolactin / Q000097:blood*; D051381:Rats
D014150:Antipsychotic Agents; D010868:Pimozide; D011388:Prolactin; D002069:Butaclamol; D002746:Chlorpromazine; D010646:Phentolamine