Quinolinic acid stimulates luteinizing hormone secretion through a serotonin-dependent mechanism

Mahlon Johnson, B. L. Carroll, W. O. Whetsell, W. R. Crowley

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 μl 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-β-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. Similarly, the administration of the serotonin antagonist, methysergide, and reduction of brain 5-HT induced by injections of 5,7 DHT in the vicinity of raphe nuclei also attentuated QUIN's stimulatory effect on LH. In contrast, depletion of brain NE and E did not significantly affect the release of LH in response to either QUIN or NMA. These findings suggest that QUIN stimulates LH secretion through mechanisms dependent on the activation of serotonergic neurons projecting from the raphe nuclei. The release of LH induced by the synthetic agonist, NMA, appears to be independent of brain monoamines.

Original languageEnglish (US)
Pages (from-to)62-67
Number of pages6
JournalExperimental Brain Research
Volume59
Issue number1
DOIs
StatePublished - Jun 1 1985
Externally publishedYes

Fingerprint

Quinolinic Acid
Luteinizing Hormone
Serotonin
Methysergide
Brain
Serotonergic Neurons
Serotonin Antagonists
Raphe Nuclei
Dihydroxytryptamines
Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide
Norepinephrine
5,7-Dihydroxytryptamine
Injections
Glutamate Receptors
N-Methylaspartate
Mixed Function Oxygenases
Aspartic Acid
Synaptic Transmission
Tryptophan
Liquid Chromatography

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Quinolinic acid stimulates luteinizing hormone secretion through a serotonin-dependent mechanism. / Johnson, Mahlon; Carroll, B. L.; Whetsell, W. O.; Crowley, W. R.

In: Experimental Brain Research, Vol. 59, No. 1, 01.06.1985, p. 62-67.

Research output: Contribution to journalArticle

Johnson, Mahlon ; Carroll, B. L. ; Whetsell, W. O. ; Crowley, W. R. / Quinolinic acid stimulates luteinizing hormone secretion through a serotonin-dependent mechanism. In: Experimental Brain Research. 1985 ; Vol. 59, No. 1. pp. 62-67.
@article{0ee3ce7ec7ba41d19ea84628a256e138,
title = "Quinolinic acid stimulates luteinizing hormone secretion through a serotonin-dependent mechanism",
abstract = "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 μl 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-β-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. Similarly, the administration of the serotonin antagonist, methysergide, and reduction of brain 5-HT induced by injections of 5,7 DHT in the vicinity of raphe nuclei also attentuated QUIN's stimulatory effect on LH. In contrast, depletion of brain NE and E did not significantly affect the release of LH in response to either QUIN or NMA. These findings suggest that QUIN stimulates LH secretion through mechanisms dependent on the activation of serotonergic neurons projecting from the raphe nuclei. The release of LH induced by the synthetic agonist, NMA, appears to be independent of brain monoamines.",
author = "Mahlon Johnson and Carroll, {B. L.} and Whetsell, {W. O.} and Crowley, {W. R.}",
year = "1985",
month = "6",
day = "1",
doi = "10.1007/BF00237666",
language = "English (US)",
volume = "59",
pages = "62--67",
journal = "Experimental Brain Research",
issn = "0014-4819",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Quinolinic acid stimulates luteinizing hormone secretion through a serotonin-dependent mechanism

AU - Johnson, Mahlon

AU - Carroll, B. L.

AU - Whetsell, W. O.

AU - Crowley, W. R.

PY - 1985/6/1

Y1 - 1985/6/1

N2 - 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 μl 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-β-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. Similarly, the administration of the serotonin antagonist, methysergide, and reduction of brain 5-HT induced by injections of 5,7 DHT in the vicinity of raphe nuclei also attentuated QUIN's stimulatory effect on LH. In contrast, depletion of brain NE and E did not significantly affect the release of LH in response to either QUIN or NMA. These findings suggest that QUIN stimulates LH secretion through mechanisms dependent on the activation of serotonergic neurons projecting from the raphe nuclei. The release of LH induced by the synthetic agonist, NMA, appears to be independent of brain monoamines.

AB - 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 μl 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-β-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. Similarly, the administration of the serotonin antagonist, methysergide, and reduction of brain 5-HT induced by injections of 5,7 DHT in the vicinity of raphe nuclei also attentuated QUIN's stimulatory effect on LH. In contrast, depletion of brain NE and E did not significantly affect the release of LH in response to either QUIN or NMA. These findings suggest that QUIN stimulates LH secretion through mechanisms dependent on the activation of serotonergic neurons projecting from the raphe nuclei. The release of LH induced by the synthetic agonist, NMA, appears to be independent of brain monoamines.

UR - http://www.scopus.com/inward/record.url?scp=0022262670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022262670&partnerID=8YFLogxK

U2 - 10.1007/BF00237666

DO - 10.1007/BF00237666

M3 - Article

VL - 59

SP - 62

EP - 67

JO - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

IS - 1

ER -