Publication Date


First Advisor

Shkelzen Shabani


Innate avidity for methamphetamine (MA) use is influenced by sensitivity to its rewarding and aversive effects. MA induces these effects through release of the neurotransmitter dopamine, stimulating dopamine D2 receptors (D2R). The contribution of D2R to MA-induced motivational effects is poorly understood. In this study, we investigated motivational effects of D2R activation by using mice selectively bred for low MA drinking (MALDR) and high MA drinking (MAHDR). In a condition place preference (CPP) procedure, doses of 0.01, 0.1, and 0.5 mg/kg quinpirole, a D2R agonist, were paired with specific environmental cues; mice were later tested for cue preference. In both lines, quinpirole dose-dependently induced significant aversion and suppressed locomotor activity. MALDR mice alone showed enhanced locomotion in a drug-free CPP test. This study suggests that D2R plays a central role in the aversive effects of MA and is a potential therapeutic target for curbing MA intake.