Nicotinic agonists administered into the fourth ventricle stimulate norepinephrine secretion in the hypothalamic paraventricular nucleus

An in vivo microdialysis study

Shannon G. Matta, John G. McCoy, Catharine A. Foster, Burt Sharp

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Nicotinic cholinergic agonists stimulate ACTH secretion by a central mechanism involving brainstem catecholamines. In vivo microdialysis studies were conducted to measure the release of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) in response to the administration of nicotine (Nic) or another nicotinic cholinergic (NAch) agonist, cytisine (Cyt), directly into the IVth ventricle. Alert, freely mobile rats, equipped 24 h previously with a chronic guide cannula in the IVth ventricle and microdialysis probe in the PVN, were injected with artificial cerebrospinal fluid (CSF, 500 nl/60 s), Nic (1–5 µg), or Cyt (1–25 µg) after three 20-min baseline samples had been taken. Analysis of the dialysates by HPLC with electrochemical detection demonstrated the dose-dependent secretion of PVN NE to Nic or Cyt with ED50s of approximately 1 or 6 µg, respectively, these were completely blocked by prior IVth ventricular injection of the NAch antagonist, mecamylamine (4 µg). In contrast, α-bungarotoxin, which antagonizes the action of NAch agonists by acting through the α7bungarotoxin-type NAchR, failed to reduce the NE response to Nic. Partial, but significant desensitization of NE secretion in response to a second injection of Nic (2.5 or 5 µg) 100 min after the first was seen, whereas NE responses to the second injection of Cyt (5 or 25 µg) were completely desensitized. However, cross-desensitization of each agonist to the other did not occur. This may reflect heterogeneity of the NAch receptor subtypes involved. The results of this study establish a correlation between the action of nicotine on brainstem norepineph-rinergic regions and the resultant release of NE in the PVN, which would lead to the release of ACTH secretagogues.

Original languageEnglish (US)
Pages (from-to)383-392
Number of pages10
JournalNeuroendocrinology
Volume61
Issue number4
DOIs
StatePublished - Jan 1 1995

Fingerprint

Nicotinic Agonists
Fourth Ventricle
Paraventricular Hypothalamic Nucleus
Microdialysis
Nicotine
Norepinephrine
Adrenocorticotropic Hormone
Injections
Brain Stem
Mecamylamine
Bungarotoxins
Dialysis Solutions
Catecholamines
Cerebrospinal Fluid
High Pressure Liquid Chromatography
cytisine

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Nicotinic agonists administered into the fourth ventricle stimulate norepinephrine secretion in the hypothalamic paraventricular nucleus : An in vivo microdialysis study. / Matta, Shannon G.; McCoy, John G.; Foster, Catharine A.; Sharp, Burt.

In: Neuroendocrinology, Vol. 61, No. 4, 01.01.1995, p. 383-392.

Research output: Contribution to journalArticle

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abstract = "Nicotinic cholinergic agonists stimulate ACTH secretion by a central mechanism involving brainstem catecholamines. In vivo microdialysis studies were conducted to measure the release of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) in response to the administration of nicotine (Nic) or another nicotinic cholinergic (NAch) agonist, cytisine (Cyt), directly into the IVth ventricle. Alert, freely mobile rats, equipped 24 h previously with a chronic guide cannula in the IVth ventricle and microdialysis probe in the PVN, were injected with artificial cerebrospinal fluid (CSF, 500 nl/60 s), Nic (1–5 µg), or Cyt (1–25 µg) after three 20-min baseline samples had been taken. Analysis of the dialysates by HPLC with electrochemical detection demonstrated the dose-dependent secretion of PVN NE to Nic or Cyt with ED50s of approximately 1 or 6 µg, respectively, these were completely blocked by prior IVth ventricular injection of the NAch antagonist, mecamylamine (4 µg). In contrast, α-bungarotoxin, which antagonizes the action of NAch agonists by acting through the α7bungarotoxin-type NAchR, failed to reduce the NE response to Nic. Partial, but significant desensitization of NE secretion in response to a second injection of Nic (2.5 or 5 µg) 100 min after the first was seen, whereas NE responses to the second injection of Cyt (5 or 25 µg) were completely desensitized. However, cross-desensitization of each agonist to the other did not occur. This may reflect heterogeneity of the NAch receptor subtypes involved. The results of this study establish a correlation between the action of nicotine on brainstem norepineph-rinergic regions and the resultant release of NE in the PVN, which would lead to the release of ACTH secretagogues.",
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