Abstinence from chronic cocaine self-administration alters striatal dopamine systems in rhesus monkeys

Neuropsychopharmacology. 2009 Apr;34(5):1162-71. doi: 10.1038/npp.2008.135. Epub 2008 Sep 3.

Abstract

Although dysregulation within the dopamine (DA) system is a hallmark feature of chronic cocaine exposure, the question of whether these alterations persist into abstinence remains largely unanswered. Nonhuman primates represent an ideal model in which to assess the effects of abstinence on the DA system following chronic cocaine exposure. In this study, male rhesus monkeys self-administered cocaine (0.3 mg/kg per injection, 30 reinforcers per session) under a fixed-interval 3-min schedule for 100 days followed by either 30 or 90 days abstinence. This duration of cocaine self-administration has been previously shown to decrease DA D2-like receptor densities and increase levels of D1-like receptors and DA transporters (DAT). Responding by control monkeys was maintained by food presentation under an identical protocol and the same abstinence periods. [(3)H]SCH 23390 binding to DA D1 receptors following 30 days of abstinence was significantly higher in all portions of the striatum, compared to control animals, whereas [(3)H]raclopride binding to DA D2 receptors was not different between groups. [(3)H]WIN 35 428 binding to DAT was also significantly higher throughout virtually all portions of the dorsal and ventral striatum following 30 days of abstinence. Following 90 days of abstinence, however, levels of DA D1 receptors and DAT were not different from control values. Although these results indicate that there is eventual recovery of the separate elements of the DA system, they also highlight the dynamic nature of these components during the initial phases of abstinence from chronic cocaine self-administration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / toxicity
  • Cocaine / administration & dosage*
  • Cocaine / analogs & derivatives
  • Cocaine / pharmacology
  • Cocaine / toxicity
  • Cocaine-Related Disorders / physiopathology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine Uptake Inhibitors / pharmacology
  • Macaca mulatta
  • Male
  • Raclopride / pharmacology
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Self Administration
  • Tritium

Substances

  • Benzazepines
  • Central Nervous System Stimulants
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • SCH 23390
  • Tritium
  • Raclopride
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • Cocaine
  • Dopamine