Enhanced morphine preference following prolonged abstinence: association with increased Fos expression in the extended amygdala.
We previously found that chronically morphine-pretreated, abstinent rats show stronger preferences for morphine-associated environments than placebo-pretreated rats. Here we show that this increased preference persisted for at least 5 weeks after withdrawal of chronic morphine. To determine brain regions involved in this behavior, we examined neural activation (as indexed by Fos-like proteins) induced by a morphine-conditioned place preference test. Placebo-pretreated (P) morphine-conditioned rats showed significantly elevated Fos in the anterior cingulate cortex (Cg), nucleus accumbens core (Ac-C) and shell (Ac-S), ventral lateral and dorsal lateral bed nucleus of the stria terminialis (BNST-VL and -DL), and central and basolateral amygdala nuclei (ACE, ABL) when compared to nonconditioned P rats. Chronically morphine-pretreated (M) rats that exhibited enhanced morphine preference 5 weeks after morphine withdrawal showed significantly greater Fos in all the same areas except the BNST-DL relative to conditioned P or nonconditioned M rats. Place preference measures and Fos expression were positively correlated in the Cg and ABL, for conditioned P animals, and in the Cg, ABL and BNST-VL for conditioned M animals. These results indicate a relationship between place preference behavior and neural indices of activation in the forebrain in response to morphine-conditioned cues that may be chronically modulated by prior morphine exposure.
Harris
Glenda C
GC
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aston-Jones
Gary
G
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism* / Q000523:psychology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology
D016760:Proto-Oncogene Proteins c-fos