Present address: Internal Research Program, NIDA, Baltimore, MD 21222, USA.
Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbens
Article first published online: 9 OCT 2008
European Journal of Neuroscience
Volume 12, Issue 4, pages 1501–1508, April 2000
How to Cite
Dunworth, S. J., Mead, A. N. and Stephens, D. N. (2000), Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbens. European Journal of Neuroscience, 12: 1501–1508. doi: 10.1046/j.1460-9568.2000.00036.x
- Issue published online: 9 OCT 2008
- Article first published online: 9 OCT 2008
- Received 3 November 1999, revised 18 January 2000, accepted 19 January 2000
- conditioned place aversion;
- conditioned taste aversion;
- repeated withdrawal;
- seizure sensitivity
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.