Decreased presynaptic sensitivity to adenosine after cocaine withdrawal

Olivier Manzoni, Didier Pujalte, John Williams, Joël Bockaert

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

The nucleus accumbens (NAc) is a site mediating the rewarding properties of drugs of abuse, such as cocaine, amphetamine, opiates, nicotine, and alcohol (Wise and Bozarth, 1987; Koob, 1992; Samson and Harris, 1992; Woolverton and Johnson, 1992; Self and Nestler, 1995; Pontieri et al., 1996). Acute cocaine has been shown to decrease excitatory synaptic transmission mediated by the cortical afferents to the NAc (Nicola et al., 1996), but the effects of long-term cocaine treatment and withdrawal have not been explored. Here, we report that long-term (1 week) withdrawal from chronic cocaine reduced the potency of adenosine to presynaptically inhibit glutamate (Glu) release by activating adenosine A1 receptors. Adenosine A1 receptors were not desensitized, because the potency of the metabolically stable adenosine analog N6-cyclopentyl-adenosine was unchanged after chronic cocaine withdrawal. When adenosine transporters were blocked, the potency of adenosine to inhibit Glu release from naive and cocaine-withdrawn NAc slices was similar. These results suggest that one of the long-term consequences of cocaine withdrawal is an augmented uptake of adenosine. This long-lasting change expressed at the presynaptic excitatory inputs to the medium spiny output neurons in the NAc may help identify new therapeutic targets for the treatment of drug abuse.

Original languageEnglish (US)
Pages (from-to)7996-8002
Number of pages7
JournalJournal of Neuroscience
Volume18
Issue number19
DOIs
StatePublished - Oct 1 1998

Keywords

  • Adenosine
  • Chronic cocaine
  • Drug abuse
  • Nucleus accumbens
  • Transporter
  • Withdrawal

ASJC Scopus subject areas

  • Neuroscience(all)

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