Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors.

摘要: Abstract Aims The dopamine D3 receptor (D3R) is a pharmacotherapeutic target for drug dependence. We have successfully imaged human D3Rs using radiolabeled LS-3-134, an arylamide phenylpiperazine with moderate selectivity the D3R over D2R and low efficacy at D2 D3R. In this study, we screened effects of LS-3-134 as potential anti-cocaine therapeutic. Methods Male rats were pretreated (0, 1.0, 3.2, or 5.6 mg/kg, IP) 15 min prior to tests its on spontaneous cocaine-induced locomotion. next investigated 5.6, 10.0 mg/kg, operant responding multiple variable-interval (VI) 60-second schedule alternating cocaine (0.375 mg/kg, IV) sucrose (45 mg) reinforcer components. Additionally, tested (5.6 mg/kg, progressive ratio (PR) reinforcement, extinction cocaine-seeking behavior, reinstatement extinguished behavior by cocaine-associated light/tone cues. Results did not alter locomotion, but reduced break points high-effort during cue reinstatement. contrast, reinforcement low-effort VI schedule. Conclusions are similar other partial agonists antagonists in attenuating intake under high effort schedules elicited These findings consistent anti-craving profile drugs.