Dopamine antagonists reduce selection of reinforcers that require vikgor: correlation with DARPP32

Abstract

Introduction: Dopamine (DA) is a neurotransmitter that is involved in vigor, persistence and work output in normal motivation. In fact, nucleus accumbens (Nacb) DA is a critical component of the neural circuitry that regulates behavioral activation, and effort-based decision-making. An imbalance of this system produces several motivational symptoms such as anergia or fatigue, seen in pathologies like depression. In animal models, DA receptor antagonists reallocate instrumental behavior away from tasks that require high levels of activation to low-effort tasks. Objective: We evaluate the impact of DA receptor antagonism (D1, D2 and D3 receptors) on performance of a decision-making task for the assessment of reinforcer preferences; the T-maze RW-sucrose pellets-odor choice task. We also assessed the impact on preferences of changing the value of the reinforcers. Methods: CD1 male mice received Ecopipam, a D1 receptor antagonist (ECO, 0.2 mg/kg), Raclopride, a D2 receptor antagonist (RACLO, 0.75 mg/kg), or SB277011A, a D3 receptor antagonist (SB, 1.5 mg/kg) and were assessed in the T-maze. DA receptor-activity-related markers (pDARPP32-Thr75 and Thr34) in Nacb were assessed using immunoblotting. Results: All DA antagonists decreased time running but only ECO and SB increased time eating. These behavioral effects were parallel to pDARPP-32(Thr34) changes. Also, the bright light over the RW, increasing resistance in the RW, and using social odors reduced time spent running, but the pattern of effects was very different to the pattern observed for DA antagonists. Conclusions: This pilot study suggest that DA receptor antagonists could induce a shift towards more sedentary sources of reinforcement that is paralleled by pDARPP-32(Thr34) changes.