Discriminative stimulus effects of cocaine: Antagonism by dopamine D1 receptor blockade in the amygdala

Patrick M. Callahan, Suzanne K. Bryan, Kathryn Cunningham

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Mesolimbic dopamine (DA) D1 and D2 receptors appear to be involved in mediating the discriminative stimulus effects of cocaine. The purpose of the present study was to investigate the role of the amygdala and, in particular, central amygdala DA D1 receptors, in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-lever responding. Intracranial bilateral injections of cocaine (20-200 μg, total dose) into the central amygdala engendered, at best, a partial substitution (<60% drug-lever responding) for the systemic cocaine cue. Central amygdala microinjections of artificial cerebrospinal fluid (ACSF; 1 μl/side) or SCH 23390 (0.5-2 μg, total dose) resulted in primarily saline-appropriate responding. In antagonism tests, bilateral injections of the DA D1 receptor antagonist SCH 23390 (0.5-2 μg, total dose) into the central amygdala produced a dose-related blockade of a systemic dose of cocaine (5 mg/kg) that engendered > 85% cocaine-lever responding when given alone. Additionally, bilateral injection of a fixed dose of SCH 23390 (2 μg) into the central amygdala resulted in a rightward shift in the cocaine dose-response curve (2.5-20 mg/kg). Although administration of cocaine into the central amygdala does not mimic the systemic cocaine cue, the present results demonstrate that DA D1 receptors located within the central amygdala appear to have a modulatory role upon the discriminative stimulus properties of cocaine.

Original languageEnglish (US)
Pages (from-to)759-766
Number of pages8
JournalPharmacology, Biochemistry and Behavior
Volume51
Issue number4
DOIs
StatePublished - 1995

Fingerprint

Dopamine D1 Receptors
Amygdala
Cocaine
Substitution reactions
Injections
Dopamine D2 Receptors
Cues
Rats
Central Amygdaloid Nucleus

Keywords

  • Central amygdala
  • Cocaine
  • Dopamine D receptors
  • Drug discrimination
  • Microinjection
  • Rat
  • SCH 23390

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Pharmacology
  • Toxicology

Cite this

Discriminative stimulus effects of cocaine : Antagonism by dopamine D1 receptor blockade in the amygdala. / Callahan, Patrick M.; Bryan, Suzanne K.; Cunningham, Kathryn.

In: Pharmacology, Biochemistry and Behavior, Vol. 51, No. 4, 1995, p. 759-766.

Research output: Contribution to journalArticle

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