Infusion of alpha-2-adrenergic agents into the paraventricular and arcuate nuclei of the hypothalamus in the Siberian hamster: opposing effects on basal prolactin.
Although the alpha(2)-adrenergic receptor subtype has been shown to have a significant influence on circulating levels of prolactin (PRL), its exact role remains unclear. A multitude of studies have demonstrated that blockade of the alpha(2)-receptor can either elevate or decrease circulating levels of PRL. Alpha(2)-receptor-mediated control of both stimulatory and inhibitory arms of the PRL regulatory system may explain this discrepancy. Activation of the alpha(2)-receptor has been shown to inhibit the activity of its target cell, and therefore antagonism of the alpha(2)-receptor within a stimulatory component (e.g., paraventricular nucleus (PVN) of the hypothalamus) would theoretically have the opposite effect that it would have within an inhibitory component (arcuate nucleus of the hypothalamus). Thus, the purpose of this study was to investigate the functional role of the alpha(2)-adrenergic receptor in modulating circulating levels of PRL both at the level of the PVN and arcuate using reverse microdialysis of alpha(2)-adrenergic agents coupled with serial blood sampling in the male Siberian hamster. Male hamsters were fitted with a jugular cannula for serial blood sampling, and an indwelling microdialysis probe for intrahypothalamic drug administration between 08:00 and 10:00 h. Blood samples were collected every hour for 5 h (12:00-17:00 h). During the third sampling period, atipamezole (alpha(2)-antagonist) or medetomidine (alpha(2)-agonist) at one of three doses were infused into the PVN or the arcuate to assess effects on basal PRL. At the level of the PVN, infusion of atipamezole initiated an increase in basal PRL in a dose-dependent fashion, whereas infusion of medetomidine induced a significant decline in basal PRL in a dose-dependent fashion. In the arcuate, only the highest dose of atipamezole had an effect on PRL, and this was in the opposite direction from that seen in the PVN. Infusion of medetomidine did not have a significant effect on basal PRL levels; however, a trend toward a significant elevation was observed for the highest dose. These results suggest that the alpha(2)-receptor subtype may have opposite effects on circulating levels of PRL within the PVN and arcuate regions, and may explain why antagonism of the alpha(2)-receptor has been shown to initiate both surges and declines in basal levels of PRL.
Dodge
James C
JC
Behavioral Neuroscience Division, Psychology Department, State University of New York at Buffalo, Buffalo, N.Y., USA. jdodge@bio.umass.edu
Badura
Lori L
LL
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects*; D006224:Cricetinae; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D020926:Medetomidine / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D017111:Phodopus; D011388:Prolactin / Q000097:blood*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D011388:Prolactin; D020926:Medetomidine