Evidence that D2 receptor-mediated activation of hypothalamic tuberoinfundibular dopaminergic neurons in the male rat occurs via inhibition of tonically active afferent dynorphinergic neurons.
The purpose of the present study was to determine if D2 receptor-mediated activation of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons occurs via afferent neuronal inhibition of tonically active inhibitory dynorphinergic neurons in the male rat. To this end, the effects of either surgical deafferentation of the mediobasal hypothalamus or administration of a kappa opioid receptor agonist (U-50,488) or antagonist (nor-binaltorphimine (NOR-BNI)) on D2 receptor-mediated activation of TIDA neurons were assessed. For comparison, the activity of mesolimbic DA neurons was also determined in these studies. TIDA and mesolimbic DA neuronal activities were estimated by measuring dopamine synthesis (accumulation of 3,4-dihydroxyphenylalanine (DOPA) following decarboxylase inhibition) and metabolism (concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC)) in terminals of these neurons in the median eminence and nucleus accumbens, respectively. Intraperitoneal administration of the D2 receptor agonist quinelorane caused a dose-dependent increase in DOPAC in the median eminence and a decrease in DOPAC in the nucleus accumbens; surgical deafferentation of the mediobasal hypothalamus prevented the effect of quinelorane in the median eminence, but not the nucleus accumbens. Activation of kappa opioid receptors with U-50,488 had no effect per se, but blocked quinelorane-induced increases in median eminence DOPA. In contrast, U-50,488 had no effect on DOPA in the nucleus accumbens of either vehicle- or quinelorane-treated rats. Blockade of kappa opioid receptors with NOR-BNI increased median eminence DOPA, and prevented the stimulatory effects of quinelorane on dopamine synthesis. Administration of prolactin also increased median eminence DOPA, but did not alter the ability of quinelorane to stimulate dopamine synthesis. Neither NOR-BNI nor prolactin had any effect on DOPA in the nucleus accumbens of vehicle- or quinelorane-treated rats. These results suggest that D2 receptor-mediated activation of TIDA neurons occurs via an afferent neuronal mechanism involving, at least in part, inhibition of tonically active inhibitory dynorphinergic neurons in the male rat.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
R A
RA
Durham
J D
JD
Johnson
K E
KE
Moore
K J
KJ
Lookingland
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000344:Afferent Pathways / Q000502:physiology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004399:Dynorphins / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007033:Hypothalamus, Middle / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008032:Limbic System / Q000166:cytology / Q000502:physiology; D008297:Male; D008473:Median Eminence / Q000502:physiology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology; D011388:Prolactin / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors
D000700:Analgesics; D018491:Dopamine Agonists; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011804:Quinolines; D017448:Receptors, Dopamine D2; D017473:Receptors, Opioid, kappa; D015102:3,4-Dihydroxyphenylacetic Acid; C051844:norbinaltorphimine; D009271:Naltrexone; D004295:Dihydroxyphenylalanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D011388:Prolactin; D004296:Dopa Decarboxylase; D004298:Dopamine; C047726:quinelorane