Multiple, but not acute, infusions of cocaine alter the release of prolactin in male rats.

Hypothalamic dopamine tonically inhibits the release of prolactin (PRL) from the anterior pituitary gland. Cocaine, in turn, alters dopaminergic transmission. We compared the effects of acute and repeated injections of cocaine on the release of PRL in male rats to assess whether cocaine could affect dopaminergically mediated hormonal responses. We found that the concentration of PRL in plasma was not affected by single i.v. injections of 1, 3 or 10 mg/kg of cocaine. However, in rats infused repeatedly with 1 mg/kg of cocaine for 5 s every 12 min for 2 h over 10 days, the pre-infusion concentrations of PRL increased in a time-dependent manner whereas cocaine uniformly decreased post-infusion levels of PRL. Repeated administration of cocaine may produce long-term changes in either the tuberoinfundibular dopaminergic neurons or the adenohypophysial dopamine D2-receptors, or both. Changes in the peripheral concentration of PRL after multiple injections of cocaine and during cocaine withdrawal may reflect dopaminergic activity in the hypothalamus. In contrast, single injections of cocaine increased adrenocorticotropin (ACTH) in a dose-dependent manner whereas repeated infusions did not increase peripheral concentrations of ACTH or corticosterone. It seems that repeated injections of cocaine do not result in persistent changes in the hypothalamo-pituitary-adrenal axis.

Characterization and autoradiographic localization of TRH receptors in sections of rat brain.

Receptors for thyrotropin-releasing hormone (TRH) in rat brain have been localized autoradiographically by exposing tritium-sensitive film to sections labeled with [3H]3-Me-His2-TRH. Greatest grain density was found over certain nuclei of the amygdala, with considerable density over several other forebrain areas. Properties of TRH receptor binding in frozen sections closely resembled those of receptors in fresh membrane fragments.

Dopamine in hypophysial portal plasma and prolactin in systemic plasma of rats treated with 5-hydroxytryptamine.

Intracerebroventricularly administered 5-hydroxytryptamine (5HT) altered the release of dopamine into pituitary stalk blood and of PRL into the systemic circulation of male rats. The concentration of dopamine in pituitary stalk plasma of rats given 0.5 or 5.0 microgram 5HT was 0.32 +/- 0.06 (mean +/- SE) or 0.18 +/- 0.04 ng/ml, respectively, and was significantly less than that in vehicle-treated animals (0.80 +/- 0.04 ng/ml). Relative to the mean level of PRL in animals injected with the solvent vehicle, the mean concentration of PRL in central venous plasma of rats given 0.5 or 5.0 microgram 5HT was increased 4-fold or 13-fold, respectively. Other rats were infused iv with dopamine for 45 min. After 15 min of infusion, the mean concentration of dopamine in arterial plasma was several times that of dopamine in pituitary stalk plasma of rats not infused with dopamine. Even so, this high concentration of dopamine did not prevent the 5HT-induced release of PRL. We conclude that 5HT modulates the secretion of PRL through a stimulatory mechanism that is effective in the presence of a high plasma concentration of dopamine, a PRL-release inhibiting factor, and suggest that 5HT causes the release of a hypothalamic substance(s) that stimulates release of PRL, i.e. a PRL-releasing factor.

Neuroendocrine control of gonadotropin secretion.

Luteinizing hormone releasing hormone (LHRH), a hypothalmic peptide that is concentrated in granules of neurons, has the capacity to release gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone) from the pituitary gland. LHRH has been found in hypophysial portal blood of rats, monkeys, and rabbits. Antibodies to LHRH depress plasma LH concentrations in castrated animals and evoke testicular atrophy, but passive immunization against LHRH does not block the LH surge induced by estrogen in monkeys. Estrogens, progestin, prolactin, and dopamine have marked effects on LH secretion, yet an association between these effects and altered hypophysial portal blood concentrations of LHRH is not established. In view of the paucity of evidence demonstrating such a cause and effect relationship, two alternative proposals have become tenable. One, hormones and neurotransmitters may not alter the levels of portal blood LHRH, but rather alter the frequency of pulsatile LHRH secretion. Two, hormones, such as estrogens, progesterone, and prolactin, may alter the responsiveness of the gonadotropin-secreting cells to LHRH by affecting the secretion of dopamine.