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

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.