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Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal‐induced c‐fos expression in nucleus accumbens
Author(s) -
Dunworth Sarah J.,
Mead Andy N.,
Stephens David N.
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00036.x
Subject(s) - kindling , diazepam , drug withdrawal , nucleus accumbens , withdrawal syndrome , stimulus (psychology) , habituation , convulsant , anesthesia , aversive stimulus , seizure threshold , psychology , pharmacology , medicine , stimulation , neuroscience , anticonvulsant , receptor , central nervous system , drug , epilepsy , psychotherapist
Flumazenil (20 mg/kg, i.p.)‐precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21‐day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c‐fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli.