The Role of the Dopamine D1 Receptor in Cognition

The dopamine D1 receptor (DD1R) has been linked to cognitive functioning in various human and animal studies using diverse methods from pharmacological manipulations to brain imaging. Moreover, suboptimal or supraoptimal functioning of the DD1R has been linked to cognitive dysfunction. However, the previous research on this topic has mainly relied on correlational evidence, or the use of drugs that are not selective to the DD1R. Therefore, the current study investigated whether cognitive dysfunction is due to suboptimal functioning of the DD1R. The DD1R mutant rat (Smits et al., 2006) provides an opportunity to examine the role of the DD1R in cognitive functioning. The performance of the DD1R mutant rats was compared to that of littermate control rats (wildtypes). Across five experiments we found tentative evidence to suggest that the DD1R is necessary for normal cognitive ability. First, the DD1R mutant rats were unable to improve their performance when an egocentric strategy was required in the starmaze, using both positive and negative reinforcement. Second, compared to wildtype rats, the DD1R mutants were impaired in learning an allocentric strategy in the starmaze with positive reinforcement when they had been previously trained in an egocentric task. Third, the mutants were unable to improve when an egocentric strategy was required in the Y-maze. Finally, the DD1R mutant rats took longer than the wildtypes to reverse their learning when a baited arm was switched after two weeks of training with a different arm as the baited arm in the T-maze. Despite some of the limitations of the experiments, these initial findings suggest an impairment in cognition. Ideas for future research and applications are discussed.