D1-receptor drugs and cocaine-seeking behavior

Investigation of receptor mediation and behavioral disruption in rats

Andrea T. Alleweireldt, Kenneth F. Kirschner, Camille B. Blake, Janet Neisewander

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Rationale: Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated. Objectives: The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects. Methods: Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session. Results: The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session. Conclusions: The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.

Original languageEnglish (US)
Pages (from-to)109-117
Number of pages9
JournalPsychopharmacology
Volume168
Issue number1-2
DOIs
StatePublished - Jul 2003

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Drug-Seeking Behavior
Cocaine
Cues
Dopamine D1 Receptors
cocaine receptor
Stereotyped Behavior
Drug Receptors

Keywords

  • Conditioned reinforcement
  • D1 phospholipase receptor
  • Hypoactivity
  • Receptor specificity
  • Relapse
  • SCH-23390
  • SKF-38393
  • SKF-81297
  • Stereotyped behavior

ASJC Scopus subject areas

  • Pharmacology

Cite this

D1-receptor drugs and cocaine-seeking behavior : Investigation of receptor mediation and behavioral disruption in rats. / Alleweireldt, Andrea T.; Kirschner, Kenneth F.; Blake, Camille B.; Neisewander, Janet.

In: Psychopharmacology, Vol. 168, No. 1-2, 07.2003, p. 109-117.

Research output: Contribution to journalArticle

Alleweireldt, Andrea T. ; Kirschner, Kenneth F. ; Blake, Camille B. ; Neisewander, Janet. / D1-receptor drugs and cocaine-seeking behavior : Investigation of receptor mediation and behavioral disruption in rats. In: Psychopharmacology. 2003 ; Vol. 168, No. 1-2. pp. 109-117.
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abstract = "Rationale: Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated. Objectives: The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects. Methods: Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session. Results: The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session. Conclusions: The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.",
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