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Differential effects of the dopamine D 3 receptor antagonist PG01037 on cocaine and methamphetamine self‐administration in rhesus monkeys
Author(s) -
John William,
Newman Amy,
Nader Michael
Publication year - 2015
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.29.1_supplement.930.5
Subject(s) - quinpirole , methamphetamine , dopaminergic , self administration , agonist , antagonist , dopamine , pharmacology , psychology , dopamine agonist , potency , medicine , receptor , chemistry , biochemistry , in vitro
Within the dopaminergic system, the DA D 3 receptor (D 3 R) has been shown to mediate many of the behavioral effects of psychostimulants associated with high abuse potential. The present study sought to extend the assessment of the highly selective D 3 R antagonist PG01037 on cocaine and methamphetamine (MA) self‐administration to include a food‐drug choice procedure. Complete cocaine and MA self‐administration dose‐response curves were determined daily in each session for eight male rhesus monkeys (n=4/group). When choice was stable, monkeys received acute and five‐day treatment of PG01037 (1.0‐10 mg/kg, i.v.). Acute administration of PG01037 significantly reallocated choice behavior from cocaine to food and decreased cocaine intake, however, tolerance developed by day 5 of treatment. Up to doses that disrupted responding, MA choice and intake were not decreased following acute or 5‐day PG01037 treatment but the behavioral potency was significantly greater on MA choice compared to cocaine choice. Furthermore, using an unconditioned behavior, yawning elicited by the D 3 /D 2 R agonist quinpirole (0.003‐0.3 mg/kg) in these same monkeys, the acute efficacy of PG01037 was negatively correlated with the sensitivity to the behavioral effects of quinpirole. These data suggest (1) that efficacy of D 3 R compounds to decrease drug choice is greater in subjects with lower D 3 R, perhaps suggesting that it is percent occupancy that is the critical variable in determining efficacy and (2) differences in D 3 R activity in chronic cocaine vs. MA users. Supported by DA012460, AA007565, and NIDA‐IRP.