Cognitive flexibility, which can be measured with reversal learning, is the ability of an individual to alter their behavior in response to changing environmental conditions. Past studies have found that dopamine (DA) is released in the nucleus accumbens (NAc) during reversal learning (Radke et al., 2019, Klanker et al., 2017). The present study sought to examine the effects of manipulating DA release in the NAc on reversal learning first by using Designer Receptors Exclusively Activated by Designer Drugs (DREADD). AAVrg-hSyn-DIO-hM3Dq-mCherry (Addgene) was injected into the NAc of male and female DAT-Cre mice. Mice learned to master a basic task of discriminating between active vs. inactive nose pokes in an operant box. Once the criterion for discrimination was met, active and inactive nose-poke holes were switched (i.e., reversal). Mice were administered the ligand clozapine-n-oxide (CNO, 1.0 mg/kg) 15 min before the first reversal session, exciting DA neurons projecting to the NAc. No differences in response between control and experimental mice following CNO administration were noted. Animals were then trained to criterion (85% correct response rate and 30+ rewards) before the nose pokes were reversed again. In this second reversal, the Cre+ (experimental) animals showed a significantly greater number of errors compared to the Cre- (control) animals. In our second approach, DAT knockout (KO) mice were used. These mice have no dopamine transporter (DAT), meaning released DA is in excess due to an inability to remove it from the synapse. Unlike DAT-Cre mice, which experienced increased DA on the day of reversal, DAT KO mice allow for analysis of effects of increased DA throughout the behavioral paradigm. No significant findings were observed in DAT-KO mice across discrimination and reversal trials. These data clarify the important role that dopamine in the NAc plays in reward learning and behavioral flexibility.
Authors: Brandon Arnold, Natalie Shand, Audrey King
Faculty Advisor: Anna Radke, Psychology
Graduate Student Advisors: Sean Monroe and Elizabeth Sneddon-Yepez, Psychology
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