Blockade or stimulation of D1 dopamine receptors attenuates cue reinstatement of extinguished cocaine-seeking behavior in rats

Psychopharmacology (Berl). 2002 Jan;159(3):284-93. doi: 10.1007/s002130100904. Epub 2001 Oct 12.


Rationale: D(1) dopamine receptor antagonists and agonists attenuate cocaine reinstatement of cocaine-seeking behavior (i.e., responding in the absence of cocaine reinforcement).

Objectives: The present study investigated the effects of a D(1) antagonist (SCH-23390), partial agonist (SKF-38393), and full agonist (SKF-81297) on reinstatement of cocaine-seeking behavior elicited by presentation of cocaine-paired cues.

Methods: Rats that had been trained to self-administer cocaine with a light/tone stimulus complex paired with each infusion underwent extinction across days. After responding diminished, rats were given response-contingent access to the cocaine-paired stimulus complex. The effects of SCH-23390 (0-10.0 microg/kg), SKF-38393 (0-3.0 mg/kg), and SKF-81297 (0-3.0 mg/kg) on cue reinstatement of cocaine-seeking behavior were examined. The ability of the two D(1) agonists to independently reinstate cocaine-seeking behavior and the effects of SKF-81297 on cocaine reinstatement were also examined. To investigate the possibility of behavioral interference, the effects of SKF-38393 and SKF-81297 on grooming and stereotypy were assessed.

Results: SCH-23390 and SKF-81297, but not SKF-38393, attenuated cue reinstatement. However, while SKF-81297 dose-dependently increased response latency, SCH-23390 did not. SKF-81297 also independently reinstated responding at the two lowest doses tested while SKF-38393 had no effect. Furthermore, SKF-81297 decreased cocaine reinstatement and increased response latency only at the highest dose. Finally, stereotypy was observed at all doses of SKF-81297 that also decreased responding, although the patterns of changes in these behaviors did not completely correspond.

Conclusions: While the antagonist and full agonist produced similar effects on cocaine-seeking behavior, only the agonist increased response latency, suggesting that different processes mediate the effects of these drugs.

MeSH terms

  • Animals
  • Behavior, Addictive*
  • Benzazepines / pharmacology
  • Cocaine / pharmacology*
  • Cues*
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Grooming / drug effects
  • Grooming / physiology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, Dopamine D1 / physiology
  • Stereotyped Behavior / drug effects
  • Stereotyped Behavior / physiology


  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • SK&F 81297
  • Cocaine