Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion

Eur J Pharmacol. 2014 May 5:730:14-9. doi: 10.1016/j.ejphar.2014.02.017. Epub 2014 Feb 25.

Abstract

Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA.

Keywords: Conditioned taste aversion; Hypothalamic–pituitary–adrenal axis; Lithium chloride; c-Fos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Animals
  • Avoidance Learning / drug effects*
  • Conditioning, Psychological / drug effects*
  • Dexamethasone / pharmacology
  • Drinking
  • Extinction, Psychological / drug effects*
  • Glucocorticoids / pharmacology*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology
  • Lithium / pharmacology*
  • Lithium Chloride / pharmacology
  • Male
  • Mifepristone / pharmacology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sucrose / pharmacology
  • Taste / drug effects*
  • Taste / physiology

Substances

  • Glucocorticoids
  • Proto-Oncogene Proteins c-fos
  • Mifepristone
  • Sucrose
  • Dexamethasone
  • Lithium
  • Lithium Chloride