Ethanol seeking triggered by environmental context is attenuated by blocking dopamine D1 receptors in the nucleus accumbens core and shell in rats

Psychopharmacology (Berl). 2009 Dec;207(2):303-14. doi: 10.1007/s00213-009-1657-6. Epub 2009 Sep 25.


Rationale: Conditioned behavioral responses to discrete drug-associated cues can be modulated by the environmental context in which those cues are experienced, a process that may facilitate relapse in humans. Rodent models of drug self-administration have been adapted to reveal the capacity of contexts to trigger drug seeking, thereby enabling neurobiological investigations of this effect.

Objectives: We tested the hypothesis that dopamine transmission in the nucleus accumbens, a neural structure that mediates reinforcement, is necessary for context-induced reinstatement of responding for ethanol-associated cues.

Methods: Rats pressed one lever (active) for oral ethanol (0.1 ml; 10% v/v) in operant conditioning chambers distinguished by specific visual, olfactory, and tactile contextual stimuli. Ethanol delivery was paired with a discrete (4 s) light-noise stimulus. Responses on a second lever (inactive) were not reinforced. Behavior was then extinguished by withholding ethanol but not the discrete stimulus in a different context. Reinstatement, expressed as elevated responding for the discrete stimulus without ethanol delivery, was tested by placing rats into the prior self-administration context after administration of saline or the dopamine D1 receptor antagonist, SCH 23390 (0.006, 0.06, and 0.6 microg/side), into the nucleus accumbens core or shell.

Results: Compared with extinction responding, active lever pressing in saline-pretreated rats was enhanced by placement into the prior ethanol self-administration context. SCH 23390 dose-dependently reduced reinstatement after infusion into the core or shell.

Conclusion: These findings suggest a critical role for dopamine acting via D1 receptors in the nucleus accumbens in the reinstatement of responding for ethanol cues triggered by placement into an ethanol-associated context.

Publication types

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

MeSH terms

  • Animals
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Conditioning, Operant / drug effects
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Ethanol / administration & dosage*
  • Extinction, Psychological / drug effects
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Recurrence
  • Reinforcement Schedule
  • Self Administration


  • Benzazepines
  • Receptors, Dopamine D1
  • SCH 23390
  • Ethanol
  • Dopamine