Pharmacological evidence that neurotensin mediates prolactin-induced activation of tuberoinfundibular dopamine neurons.
The purpose of this study was to investigate the role of neurotensin (NT) receptors in mediating the stimulatory effects of prolactin on the activity of tuberoinfundibular dopamine (TIDA) neurons in male and female rats. TIDA neuronal activity was estimated by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in terminals of these neurons in the median eminence (ME). Haloperidol activates TIDA neurons indirectly by blocking D2 receptors on pituitary lactotropes, thereby increasing secretion of prolactin. Twelve hours after administration of haloperidol (1 mg/kg, s.c.), DOPAC concentrations in the ME were increased. Blockade of NT receptors with the selective antagonist SR-48692 had no effect per se on basal DOPAC concentrations in the ME but produced a dose-related (10-1,000 microg/kg, i.p.; 1 h) reversal of haloperidol-induced increases in ME DOPAC concentrations. In contrast, SR-48692 had no effect on either basal or haloperidol-induced increases in plasma prolactin. SR-48692 also blocked the stimulatory effects of prolactin (10 microg/rat, i.c.v.; 12 h) on ME DOPAC concentrations. SR-48692 was equally effective in blocking the stimulatory effects of haloperidol and prolactin on TIDA neurons in male and female rats. These results suggest that NT mediates the induced stimulatory effect of hyperprolactinemia on the activity of TIDA neurons in both males and females, whereas the tonic regulation of these neurons by prolactin in females occurs via an NT-independent mechanism.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
K
K
Hentschel
S
S
Cheung
K E
KE
Moore
K J
KJ
Lookingland
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D001667:Binding, Competitive / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008473:Median Eminence / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D009496:Neurotensin / Q000502:physiology*; D011388:Prolactin / Q000097:blood*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D012737:Sex Factors
D018492:Dopamine Antagonists; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; D015102:3,4-Dihydroxyphenylacetic Acid; C079087:SR 48692; D009496:Neurotensin; D011388:Prolactin; D006220:Haloperidol; D004298:Dopamine