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Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine

Academic Article
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Overview

authors

  • Parsons, Loren (Larry)
  • Koob, George
  • Weiss, Friedbert

publication date

  • September 1995

journal

  • Journal of Pharmacology and Experimental Therapeutics  Journal

abstract

  • To test the hypothesis that cocaine withdrawal is associated with abnormalities in serotonin (5-HT) neurotransmission, 5-HT concentrations in the nucleus accumbens (NAC) of rats were analyzed with microdialysis both during and after 12 h of unlimited-access intravenous cocaine self-administration. For comparison with previous work, dopamine (DA) levels were also monitored. Self-administration produced sustained increases of both 5-HT and DA to approximately 340% of base line. During the first 6 h of withdrawal, dialysate 5-HT concentrations decreased to 41% of base-line levels obtained before self-administration and to 25% of levels in drug-naive control animals. During the same period, dialysate DA decreased to 72% of presession base-line concentrations but did not decline below control levels. Extracellular 5-HT concentrations were subsequently estimated by use of a quantitative microdialysis technique. After 12 h of self-administration extracellular 5-HT levels were significantly lower (0.6 +/- 0.3 nM) than levels in drug-naive animals (2.0 +/- 0.5 nM) or in rats given only limited-access to cocaine (3 h/day; 1.4 +/- 0.2 nM). Additionally, after 12 h of self-administration low concentrations of intra-accumbens 5-HT applied by reverse dialysis significantly elevated DA efflux. This effect was not observed in either control animals or in rats given only limited access to cocaine. These results suggest that deficient 5-HT neurotransmission may be a significant factor in the cocaine withdrawal symptomatology and provide key information regarding nondopaminergic mechanisms involved in cocaine dependence.

subject areas

  • Animals
  • Biological Transport
  • Cocaine
  • Dialysis
  • Dopamine
  • Dopamine Uptake Inhibitors
  • Infusions, Intravenous
  • Male
  • Narcotics
  • Nucleus Accumbens
  • Rats
  • Rats, Wistar
  • Self Administration
  • Serotonin
  • Substance Withdrawal Syndrome
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Identity

International Standard Serial Number (ISSN)

  • 0022-3565

PubMed ID

  • 7562486
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Additional Document Info

start page

  • 1182

end page

  • 1191

volume

  • 274

issue

  • 3

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