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Corticosterone-attenuating and anxiolytic properties of mecamylamine in the rat.

Abstract
1. The available evidence suggests that stress induced release of acetylcholine (ACh) in the brain has a significant role in mediating neuroendocrine, emotional, and physiological responses to stress. Recent findings also suggest that stress indirectly (via acetylcholine) and nicotine directly stimulates the HPA axis through activation of nAChRs. 2. Our working hypothesis is that under stressful conditions, nicotinic receptor antagonists, such as mecamylamine, should act to attenuate the activation of the HPA axis and exhibit anxiolytic behavioral effects. The purpose of this study was to determine whether or not mecamylamine would: a) produce anxiolytic effects in rats on the elevated plus maze and b) blunt the plasma corticosterone response to predator stress in rats. 3. Results suggested that mecamylamine has anxiolytic properties under stressful conditions. In the EPM experiment, mecamylamine (0.3 mg/kg) produced increased time spent in the open arms. Similarly, in the predator stressor experiment, mecamylamine blunted the stress-induced plasma corticosterone response, with the lowest dose of mecamylamine (0.1 mg/kg). 4. These findings may have important therapeutic implications since clinical observations have shown that low doses of mecamylamine reduce tension and anxiety in patients with Tourette syndrome.
AuthorsM B Newman, S J Nazian, P R Sanberg, D M Diamond, R D Shytle
JournalProgress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 25 Issue 3 Pg. 609-20 (Apr 2001) ISSN: 0278-5846 [Print] England
PMID11371000 (Publication Type: Journal Article)
Chemical References
  • Anti-Anxiety Agents
  • Nicotinic Antagonists
  • Mecamylamine
  • Corticosterone
Topics
  • Animals
  • Anti-Anxiety Agents (pharmacology, therapeutic use)
  • Anxiety (drug therapy)
  • Cats
  • Corticosterone (blood)
  • Dose-Response Relationship, Drug
  • Hypothalamo-Hypophyseal System (drug effects, metabolism)
  • Male
  • Mecamylamine (pharmacology, therapeutic use)
  • Nicotinic Antagonists (pharmacology, therapeutic use)
  • Pituitary-Adrenal System (drug effects, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological (blood, drug therapy)

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