Nicotine elevates rat plasma ACTH by a central mechanism

J Pharmacol Exp Ther. 1987 Oct;243(1):217-26.


Nicotine is a potent secretagogue for the release of adrenocorticotropin (ACTH) from the anterior pituitary in vivo. However, the location of its action is unknown; knowledge of this is essential for elucidating its mechanism. Our studies show that cytisine, a peripherally acting nicotinic cholinergic agonist, given i.v. at doses equimolar or greater than nicotine, failed to elevate plasma ACTH levels, whereas nicotine (0.01 and 0.03 mg/kg b.wt.) had significant effects. Nicotine (10(-7)-10(-4) M) had no effect on the secretion of beta-endorphin by anterior pituicytes in vitro, nor did it potentiate the action of corticotropin-releasing factor (10(-9) or 10(-8) M). Intracerebroventricular injection of nicotine (1-20 micrograms) significantly elevated ACTH levels. Moreover, ACTH responses to nicotine delivered into the hypothalamic region of the third ventricle were significantly greater than those elicited by injection into the upper region. Additional studies were conducted to determine the earliest age at which nicotine stimulates ACTH. The response to i.p. nicotine (1 or 2 mg/kg b.wt.) was present but diminished during the postnatal period, whereas maximal responses comparable to mature rats were attained by day 15. To establish whether nicotine has a central effect in younger animals, nicotinic antagonists were tested. Hexamethonium (2 mg/kg b.wt.), a peripherally acting antagonist, was ineffective against nicotine (0.025 and 2.0 mg/kg b.wt.), whereas mecamylamine (2 mg/kg b.wt.), inhibitory at both peripheral and central sites, blocked the ACTH response. Thus, whether administered peripherally or centrally, nicotine activates central mechanisms mediating the release of ACTH; it appears that the target(s) for nicotine are within the hypothalamus or brainstem.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / metabolism*
  • Alkaloids / pharmacology
  • Animals
  • Azocines
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology
  • Corticotropin-Releasing Hormone / pharmacology*
  • Female
  • Hypothalamus / drug effects
  • Hypothalamus / physiology*
  • In Vitro Techniques
  • Injections, Intraventricular
  • Kinetics
  • Male
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Pituitary Gland, Anterior / drug effects
  • Pituitary Gland, Anterior / metabolism*
  • Quinolizines
  • Rats
  • beta-Endorphin / metabolism


  • Alkaloids
  • Azocines
  • Quinolizines
  • cytisine
  • beta-Endorphin
  • Nicotine
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone