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The role of dopamine D3 receptors in the discriminative stimulus effects of quinpirole, cocaine, and methamphetamine in rhesus monkeys
Author(s) -
Duke Angela N,
Green Heather L,
Newman Amy H,
Nader Michael A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.659.4
Subject(s) - quinpirole , agonist , dopamine receptor d3 , pharmacology , partial agonist , methamphetamine , buspirone , stimulant , dopamine agonist , receptor , dopamine , stimulus control , dopamine receptor , medicine , endocrinology , chemistry , nicotine
Dopamine (DA) D3 receptors may be a promising therapeutic target for stimulant abuse. Compounds deemed partial agonists in vitro do not typically show D3 agonist effects in vivo . It was recently reported that the D3 partial agonist PG619 elicited yawning in monkeys with an extensive cocaine history to a similar degree as the D3 agonist quinpirole (QUIN). The current experiments investigated the role of DA D3 receptors in three groups of monkeys trained to discriminate QUIN (0.03 mg/kg), cocaine (COC) or methamphetamine (MA), both at 0.1 mg/kg, in a two‐key saline versus drug discrimination (SD) paradigm. PG619 (0.3–10.0 mg/kg) did not substitute for QUIN, but enhanced QUIN‐appropriate responding when given as a pretreatment (3.0 mg/kg), indicating D3 agonist effects. Buspirone (0.03–0.3 mg/kg), a D3 antagonist, substituted for QUIN in 2 of 3 monkeys without decreasing response rates. In COC‐ and MA‐trained monkeys, QUIN did not substitute for the training dose. In preliminary studies, buspirone blocked the SD effects of COC and MA. Taken together, these findings using D3 partial agonists and antagonists suggest a unique pharmacology related to D3 receptor function and support the hypothesis that COC and MA exposure modifies these effects. These studies support the continued exploration of novel D3 receptor compounds for the treatment of stimulant abuse. DA12460, NIDA‐IRP