Quinolinic acid stimulates luteinizing hormone secretion through a serotonin-dependent mechanism.
Previous results from this laboratory suggest that the tryptophan metabolite, quinolinic acid (QUIN), stimulates luteinizing hormone (LH) secretion in female rats, most likely through actions on NMDA-preferring excitatory amino acid receptors. The present experiments examined whether QUIN alters LH secretion through actions requiring intact catecholaminergic or serotonergic mechanisms. Each study examined the effects of intracisternal (i.c.) injections of 25 microliter acidic saline or saline containing QUIN (500 nmol) or the synthetic analogue, N-methyl-DL-aspartate (NMA, 500 nmol), into ovariectomized, estradiol benzoate-primed rats after pharmacologic disruption of monoaminergic neurotransmission. In each experiment, animals were decapitated 5 min after QUIN or NMA administration. Experiment 1 examined whether reduction in brain serotonin (5-HT) or of norepinephrine (NE) and epinephrine (E) alters the QUIN- or NMA-induced stimulation of LH secretion. Rats were pretreated with the dopamine-beta-hydroxylase inhibitor, FLA-63 (40 mg/kg 2 h prior). A second experiment examined the effects of the 5-HT antagonist, methysergide, on QUIN or NMA stimulation of LH secretion. Methysergide (15 mg/kg) was administered 30 min prior to experimentation. Experiment 3 examined whether selective destruction of raphe serotonergic neurons with the indoleamine neurotoxin, 5,7 dihydroxytryptamine (5,7 DHT), alters QUIN's stimulatory effects. In each study, serum LH concentrations were determined by radioimmunoassay. Hypothalamic catecholamine and 5-HT concentrations were measured by radioenzymatic assay and liquid chromatography with electrochemical detection, respectively. Depletion of brain 5-HT with PCPA significantly reduced the stimulation of LH secretion by QUIN, but not by NMA.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
M D
MD
Carroll
B L
BL
Whetsell
W O
WO
Crowley
W R
WR
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002369:Castration; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism*; D016202:N-Methylaspartate; D009638:Norepinephrine / Q000502:physiology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D011725:Pyridines; D011805:Quinolinic Acids; D001224:Aspartic Acid; D012701:Serotonin; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; D007986:Luteinizing Hormone; D017378:Quinolinic Acid; D009638:Norepinephrine