Detection byin vivomicrodialysis of nicotine-induced norepinephrine secretion from the hypothalamicparaventricular nucleus of freely moving rats

Dose-dependency and desensitization

Burt Sharp, Shannon G. Matta

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The ACTH response to many stimuli depends on the secretion of norepinephrine, which activates neurons in the hypothalamic paraventricular nucleus (PVN). Studies with adrenergic antagonists and inhibitors of catecholamine synthesis indicate that norepinephrine is amediator of nicotine-induced ACTH secretion. To directly assess theeffect of nicotine on PVN norepinephrine secretion, in vivomicrodialysis was performed. Nicotine (0.5 mg/kg BW, ip) induced peaknorepinephrine levels within 20 min (-2 x basal). The central nicotinicreceptor antagonist, mecamylamine, abolished this response, whereashexamethonium, a peripheral antagonist, was ineffective. The norepinephrine response was dose dependent (ED50, -0.25 mg/kg), and nicotine (0.5 mg/kg BW) induced maximal secretion. Rapid desensitization occurred, as evidenced by a significant reduction (-50%) in theresponse to a second injection of nicotine (0.5 mg/kg BW). Animalsalso received four injections of nicotine to determine whether repetitivedosing leads to progressive reduction of the norepinephrine response.The responses to the third and fourth nicotine injections were similar.Thus, desensitization occurred after a single exposure to nicotine andwas not progressive. In contrast, nicotine pretreatment did not affectthe release of norepinephrine due to yohimbine. These results indicatethat basal and nicotine-stimulated levels of norepinephrine can bedetected in microdialysates from the PVN; rapid desensitization of thenorepinephrine response to nicotine and inhibition by mecamylamine, but not hexamethonium, parallel the findings previously reported forACTH.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalEndocrinology
Volume133
Issue number1
DOIs
StatePublished - Jan 1 1993

Fingerprint

Nicotine
Norepinephrine
Paraventricular Hypothalamic Nucleus
Mecamylamine
Adrenocorticotropic Hormone
Injections
Hexamethonium
Adrenergic Antagonists
Yohimbine
Catecholamines
Neurons

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

@article{a4b26c49038743cdb06d3e03e1c7f85e,
title = "Detection byin vivomicrodialysis of nicotine-induced norepinephrine secretion from the hypothalamicparaventricular nucleus of freely moving rats: Dose-dependency and desensitization",
abstract = "The ACTH response to many stimuli depends on the secretion of norepinephrine, which activates neurons in the hypothalamic paraventricular nucleus (PVN). Studies with adrenergic antagonists and inhibitors of catecholamine synthesis indicate that norepinephrine is amediator of nicotine-induced ACTH secretion. To directly assess theeffect of nicotine on PVN norepinephrine secretion, in vivomicrodialysis was performed. Nicotine (0.5 mg/kg BW, ip) induced peaknorepinephrine levels within 20 min (-2 x basal). The central nicotinicreceptor antagonist, mecamylamine, abolished this response, whereashexamethonium, a peripheral antagonist, was ineffective. The norepinephrine response was dose dependent (ED50, -0.25 mg/kg), and nicotine (0.5 mg/kg BW) induced maximal secretion. Rapid desensitization occurred, as evidenced by a significant reduction (-50{\%}) in theresponse to a second injection of nicotine (0.5 mg/kg BW). Animalsalso received four injections of nicotine to determine whether repetitivedosing leads to progressive reduction of the norepinephrine response.The responses to the third and fourth nicotine injections were similar.Thus, desensitization occurred after a single exposure to nicotine andwas not progressive. In contrast, nicotine pretreatment did not affectthe release of norepinephrine due to yohimbine. These results indicatethat basal and nicotine-stimulated levels of norepinephrine can bedetected in microdialysates from the PVN; rapid desensitization of thenorepinephrine response to nicotine and inhibition by mecamylamine, but not hexamethonium, parallel the findings previously reported forACTH.",
author = "Burt Sharp and Matta, {Shannon G.}",
year = "1993",
month = "1",
day = "1",
doi = "10.1210/endo.133.1.8391419",
language = "English (US)",
volume = "133",
pages = "11--19",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Detection byin vivomicrodialysis of nicotine-induced norepinephrine secretion from the hypothalamicparaventricular nucleus of freely moving rats

T2 - Dose-dependency and desensitization

AU - Sharp, Burt

AU - Matta, Shannon G.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - The ACTH response to many stimuli depends on the secretion of norepinephrine, which activates neurons in the hypothalamic paraventricular nucleus (PVN). Studies with adrenergic antagonists and inhibitors of catecholamine synthesis indicate that norepinephrine is amediator of nicotine-induced ACTH secretion. To directly assess theeffect of nicotine on PVN norepinephrine secretion, in vivomicrodialysis was performed. Nicotine (0.5 mg/kg BW, ip) induced peaknorepinephrine levels within 20 min (-2 x basal). The central nicotinicreceptor antagonist, mecamylamine, abolished this response, whereashexamethonium, a peripheral antagonist, was ineffective. The norepinephrine response was dose dependent (ED50, -0.25 mg/kg), and nicotine (0.5 mg/kg BW) induced maximal secretion. Rapid desensitization occurred, as evidenced by a significant reduction (-50%) in theresponse to a second injection of nicotine (0.5 mg/kg BW). Animalsalso received four injections of nicotine to determine whether repetitivedosing leads to progressive reduction of the norepinephrine response.The responses to the third and fourth nicotine injections were similar.Thus, desensitization occurred after a single exposure to nicotine andwas not progressive. In contrast, nicotine pretreatment did not affectthe release of norepinephrine due to yohimbine. These results indicatethat basal and nicotine-stimulated levels of norepinephrine can bedetected in microdialysates from the PVN; rapid desensitization of thenorepinephrine response to nicotine and inhibition by mecamylamine, but not hexamethonium, parallel the findings previously reported forACTH.

AB - The ACTH response to many stimuli depends on the secretion of norepinephrine, which activates neurons in the hypothalamic paraventricular nucleus (PVN). Studies with adrenergic antagonists and inhibitors of catecholamine synthesis indicate that norepinephrine is amediator of nicotine-induced ACTH secretion. To directly assess theeffect of nicotine on PVN norepinephrine secretion, in vivomicrodialysis was performed. Nicotine (0.5 mg/kg BW, ip) induced peaknorepinephrine levels within 20 min (-2 x basal). The central nicotinicreceptor antagonist, mecamylamine, abolished this response, whereashexamethonium, a peripheral antagonist, was ineffective. The norepinephrine response was dose dependent (ED50, -0.25 mg/kg), and nicotine (0.5 mg/kg BW) induced maximal secretion. Rapid desensitization occurred, as evidenced by a significant reduction (-50%) in theresponse to a second injection of nicotine (0.5 mg/kg BW). Animalsalso received four injections of nicotine to determine whether repetitivedosing leads to progressive reduction of the norepinephrine response.The responses to the third and fourth nicotine injections were similar.Thus, desensitization occurred after a single exposure to nicotine andwas not progressive. In contrast, nicotine pretreatment did not affectthe release of norepinephrine due to yohimbine. These results indicatethat basal and nicotine-stimulated levels of norepinephrine can bedetected in microdialysates from the PVN; rapid desensitization of thenorepinephrine response to nicotine and inhibition by mecamylamine, but not hexamethonium, parallel the findings previously reported forACTH.

UR - http://www.scopus.com/inward/record.url?scp=0027301754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027301754&partnerID=8YFLogxK

U2 - 10.1210/endo.133.1.8391419

DO - 10.1210/endo.133.1.8391419

M3 - Article

VL - 133

SP - 11

EP - 19

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 1

ER -