Discriminative stimulus effects of cocaine: antagonism by dopamine D1 receptor blockade in the amygdala.
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 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 micrograms, 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 microliter/side) or SCH 23390 (0.5-2 microgram, total dose) resulted in primarily saline-appropriate responding. In antagonism tests, bilateral injections of the DA D1 receptor antagonist SCH 23390 (0.5-2 microgram, 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 micrograms) 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.
Callahan
P M
PM
University of Texas Medical Branch, Department of Pharmacology and Toxicology J-31, Galveston 77555-1031, USA.
Bryan
S K
SK
Cunningham
K A
KA
D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D003042:Cocaine