Prolactin regulation of tuberoinfundibular dopaminergic neurons: immunoneutralization studies

The purpose of this study was to determine the effects of acute hypoprolact inemia on tuberoinfundibular dopamine (DA) neurons using a rabbit anti-rat prolactin antiserum (PRL-AB) to immunoneutralize circulating prolactin unde r basal conditions and at various times after haloperidol-induced hyperprol actinemia. The specificity of PRL-AB for prolactin was determined by examin ing the ability of unlabelled hormone to displace binding of I-125-labelled prolactin to PRL-AB. Tuberoinfundibular DA neuronal activity was estimated by measuring the concentrations of the DA metabolite 3,4-dihydroxyphenylac etic acid (DOPAC) in the median eminence which contains terminals of these neurons. Systemic (i.v.) administration of 200 mu l of PRL-AB decreased pla sma prolactin concentrations below detectable levels for at least 4 h. and this was accompanied by a pronounced decrease in DOPAC concentrations in th e median eminence of females, but not males. Central (i.c.v.) administratio n of 2 mu l PRL-AB diluted up to 1:100 mimicked the inhibitory effect of sy stemic administration of PRL-AB on median eminence DOPAC concentrations sug gesting that the tonic stimulatory effect of prolactin on the basal activit y of tuberoinfundibular DA neurons in females occurs via a central site of action. In male rats, blockade of anterior pituitary DA receptors with halo peridol (1 mg/kg: s.c.) caused an prompt (by 1 h) increase in plasma prolac tin concentrations which was maintained for at least 12 h. Haloperidol-indu ced hyperprolactinemia also caused a delayed (at 6 and 12 h) increase in me dian eminence DOPAC concentrations in these animals which was blocked by PR L-AB, Exposure of rats to initial printing periods of endogenous hyperprola ctinemia of up to 6 h duration (followed by 6 h or more of PRL-AB-induced h ypoprolactinemia) failed to alter median eminence DOPAC concentrations unle ss prolactin exposure was reinstated by an i.c.v. injection of prolactin, T hese results confirm that prolactin mediates the stimulatory effects of hal operidol on tuberoinfundibular DA neurons, and reveal that delayed induced activation of these neurons by prolactin is dependent upon a priming period of sustained hyperprolactinemia longer than 3 h for initiation and mainten ance of this response. (C) 2000 Elsevier Science B.V. AU rights reserved.