Prolactin regulation of tuberoinfundibular dopaminergic neurons: immunoneutralization studies.
The purpose of this study was to determine the effects of acute hypoprolactinemia on tuberoinfundibular dopamine (DA) neurons using a rabbit anti-rat prolactin antiserum (PRL-AB) to immunoneutralize circulating prolactin under basal conditions and at various times after haloperidol-induced hyperprolactinemia. The specificity of PRL-AB for prolactin was determined by examining the ability of unlabelled hormone to displace binding of 125I-labelled prolactin to PRL-AB. Tuberoinfundibular DA neuronal activity was estimated by measuring the concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence which contains terminals of these neurons. Systemic (i.v.) administration of 200 microl of PRL-AB decreased plasma prolactin concentrations below detectable levels for at least 4 h, and this was accompanied by a pronounced decrease in DOPAC concentrations in the median eminence of females, but not males. Central (i.c.v.) administration of 2 microl PRL-AB diluted up to 1:100 mimicked the inhibitory effect of systemic administration of PRL-AB on median eminence DOPAC concentrations suggesting that the tonic stimulatory effect of prolactin on the basal activity of tuberoinfundibular DA neurons in females occurs via a central site of action. In male rats, blockade of anterior pituitary DA receptors with haloperidol (1 mg/kg; s.c.) caused an prompt (by 1 h) increase in plasma prolactin concentrations which was maintained for at least 12 h. Haloperidol-induced hyperprolactinemia also caused a delayed (at 6 and 12 h) increase in median eminence DOPAC concentrations in these animals which was blocked by PRL-AB. Exposure of rats to initial priming periods of endogenous hyperprolactinemia of up to 6 h duration (followed by 6 h or more of PRL-AB-induced hypoprolactinemia) failed to alter median eminence DOPAC concentrations unless prolactin exposure was reinstated by an i.c.v. injection of prolactin. These results confirm that prolactin mediates the stimulatory effects of haloperidol 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 maintenance of this response.
Hentschel
K
K
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Fleckenstein
A E
AE
Toney
T W
TW
Lawson
D M
DM
Moore
K E
KE
Lookingland
K J
KJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000378:metabolism; D007106:Immune Sera / Q000276:immunology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011388:Prolactin / Q000097:blood / Q000276:immunology / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D011954:Receptors, Dopamine / Q000378:metabolism
D018492:Dopamine Antagonists; D007106:Immune Sera; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D011388:Prolactin; D006220:Haloperidol; D004298:Dopamine