title: Activation of the hypothalamic-pituitary-adrenal axis in lithium-induced conditioned taste aversion learning.
abstract: Intraperitoneal injections (ip) of lithium chloride at large doses induce c-Fos expression in the brain regions implicated in conditioned taste aversion (CTA) learning, and also activate the hypothalamic-pituitary-adrenal (HPA) axis and increase the plasma corticosterone levels in rats. A pharmacologic treatment blunting the lithium-induced c-Fos expression in the brain regions, but not the HPA axis activation, induced CTA formation. Synthetic glucocorticoids at conditioning, but not glucocorticoid antagonist, attenuated the lithium-induced CTA acquisition. The CTA acquisition by ip lithium was not affected by adrenalectomy regardless of basal corticosterone supplement, but the extinction was delayed in the absence of basal corticosterone. Glucocorticoids overloading delayed the extinction memory formation of lithium-induced CTA. ip lithium consistently induced the brain c-Fos expression, the HPA activation and CTA formation regardless of the circadian activation of the HPA axis. Intracerebroventricular (icv) injections of lithium at day time also increased the brain c-Fos expression, activated the HPA axis and induced CTA acquisition. However, icv lithium at night, when the HPA axis shows its circadian activation, did not induce CTA acquisition nor activate the HPA axis, although it increased the brain c-Fos expression. These results suggest that the circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA learning in rats, and the HPA axis activation may be necessary for the central effect of lithium in CTA formation. Also, glucocorticoids may be required for a better extinction; however, increased glucocorticoids hinder both the acquisition and the extinction of lithium-induced CTA.
authors.affiliation: Dental Research Institute, Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, Seoul 110-768, Republic of Korea. Electronic address: jwjahng@snu.ac.kr.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jahng
authors.affiliation: Dental Research Institute, Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, Seoul 110-768, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008094:Lithium / Q000494:pharmacology*; D013649:Taste / Q000502:physiology*
chemical_list: D008094:Lithium
keywords: Aversive taste learning; Glucocorticoid, Lithium chloride; Hypothalamic-pituitary-adrenal axis