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Drugs Acting on Autonomic Ganglia: Stimulants01:23

Drugs Acting on Autonomic Ganglia: Stimulants


Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
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Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
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Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
10:04

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

Published on: October 29, 2012

Enhanced nicotinic receptor function and drug abuse vulnerability.

Zara M Fagen1, Robert Mitchum, Paul Vezina

  • 1Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 19, 2007
PubMed
Summary

Individual differences in novelty-seeking behavior correlate with nicotinic acetylcholine receptor (nAChR) function, influencing drug abuse vulnerability. Stress hormones and nAChR activity in the brain

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Area of Science:

  • Neuroscience
  • Behavioral Pharmacology
  • Addiction Research

Background:

  • Individual differences in vulnerability to drug abuse are well-documented in humans and animals.
  • High activity in novel environments is linked to increased psychostimulant self-administration.
  • Nicotinic acetylcholine receptor (nAChR) activity is implicated in the rewarding effects of addictive drugs.

Purpose of the Study:

  • To investigate the hypothesis that variations in nAChR activity contribute to individual predispositions for drug self-administration.
  • To explore the relationship between behavioral responses to novelty, nAChR function, and stress hormones.

Main Methods:

  • Adult rats were screened for novelty response.
  • Electrophysiological measurements of nAChR function were performed in brain slices containing ventral tegmental area (VTA) dopamine neurons.
  • Effects of corticosterone treatment and chronic stress on nAChR responses were assessed in vitro and in vivo.
  • Involvement of steroid hormone receptors was examined using RU486 pretreatment.

Main Results:

  • A positive correlation was found between novelty response and nAChR function, affecting synaptic inputs and neuronal responses in the VTA.
  • Novelty response and drug sensitivity correlated positively with the hormonal stress response.
  • nAChR responses were enhanced by corticosterone and stress, an effect blocked by RU486, indicating steroid hormone receptor involvement.

Conclusions:

  • Individual differences in nAChR function within the mesoaccumbens dopamine system may underlie variations in drug abuse vulnerability.
  • These differences are likely linked to individual variations in stress hormone levels.
  • The findings highlight a potential neurobiological mechanism connecting stress, nAChR activity, and addiction susceptibility.