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, chlorproma zine 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 d-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 (0.063 mg/kg), pimozide stimulated a significant increase in prolactin in lesioned rats. The involvement of an α-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 hypothalamic-lesioned rats possibly by blocking the inhibitory action of dopamine from nonhypothalamic sources, or by releasing a substance which possesses prolactin-releasing activity.
- Hypothalamic lesions
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Cellular and Molecular Neuroscience
- Endocrine and Autonomic Systems