title: Cocaine-induced membrane adaptation in the central nucleus of amygdala.
abstract: Exposure to drugs of abuse lead to both rewarding effects and the subsequent development of negative affects. The progressive dysregulation of both processes is thought to critically contribute to the addictive state. Whereas cocaine-induced maladaptations in reward circuitry have been extensively examined, the cellular substrates underlying negative affect remain poorly understood. This study focuses on the central nucleus of the amygdala (CeA), a brain region that has been implicated in negative affective states upon withdrawal from chronic cocaine use. We observed that the two major types of CeA neurons, low-threshold bursting (LTB) neurons and regular spiking (RS) neurons, exhibited different sensitivity to corticotrophin-releasing factor (CRF), a stress hormone that has been implicated in negative affect during drug withdrawal. Furthermore, LTB and RS neurons developed opposite membrane adaptations following short-term (5 day) cocaine self-administration; the membrane excitability was increased in LTB neurons but decreased in RS neurons. These short-term exposure-induced effects were transient as they were present on withdrawal day 1 but disappeared on withdrawal day 21. However, extended exposure (21 day) led to sustained increase in the membrane excitability of LTB neurons such that it lasted over 21 days into the withdrawal period. These results suggest that CeA neurons can be a cellular target for cocaine to reshape the circuitry mediating negative affects during withdrawal, and that the long-lasting cellular alterations in selective subpopulations of CeA neurons may lead to unbalanced CeA processing, thus contributing to the progressive aggravation of negative affective states during withdrawal from chronic cocaine exposure.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Yao-Ying
authors.initials: YY
authors.lastname: Ma
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiusong
authors.initials: X
authors.lastname: Wang
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
chemical_list: D003346:Corticotropin-Releasing Hormone; D003042:Cocaine