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PMID: 9742166 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Decreased presynaptic sensitivity to adenosine after cocaine withdrawal.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 18 ·No. 19 ·1998-10-01 ·Pages 7996-8002

Manzoni O, Pujalte D, Williams J, Bockaert J

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 andHarris, 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 When adenosine transporters were blocked, the potency of adenosine to inhibit Glu release from naive and cocaine-withdrawn NAc slices was similar.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.

MeSH Terms
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology Adenosine/analogs & derivatives,pharmacology Affinity Labels/pharmacology Animals Cocaine/pharmacology Dipyridamole/pharmacology Dopamine Uptake Inhibitors/pharmacology Excitatory Postsynaptic Potentials/drug effects,physiology Glutamic Acid/metabolism Hippocampus/cytology,drug effects,metabolism Male Nucleus Accumbens/cytology,drug effects,metabolism Phosphodiesterase Inhibitors/pharmacology Presynaptic Terminals/drug effects,physiology Purinergic P1 Receptor Agonists Rats Rats, Sprague-Dawley Stimulation, Chemical Substance Withdrawal Syndrome/physiopathology Substance-Related Disorders/physiopathology Theophylline/analogs & derivatives,pharmacology Thioinosine/analogs & derivatives,pharmacology Vasodilator Agents/pharmacology Xanthines/pharmacology
Chemicals
Affinity Labels Dopamine Uptake Inhibitors Phosphodiesterase Inhibitors Purinergic P1 Receptor Agonists Vasodilator Agents Xanthines 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone 8-cyclopentyl-1,3-dimethylxanthine Glutamic Acid N(6)-cyclopentyladenosine Thioinosine Dipyridamole 1,3-dipropyl-8-cyclopentylxanthine Theophylline 4-nitrobenzylthioinosine Cocaine Adenosine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Manzoni O
Centre National de la Recherche Scientifique, Unité Propre de Recherches 9023, 34094 Montpellier Cedex 05, France.
Pujalte D
Williams J
Bockaert J
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-10-01
Pages
7996-8002
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6792995
Subset
IM
Grants
NIDA NIH HHS · R01 DA004523 · United States
NIDA NIH HHS · DA04523 · United States
External Links
PubMed source PMC Full Text View journal details
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