The Role of the Dopamine D₁ Receptor in the Negative Symptoms of Schizophrenia

Abstract

Diminished motivation is a core feature of schizophrenia that has been linked to impaired functional outcomes. A mechanism thought to contribute to diminished motivation is impaired anticipatory pleasure. Impaired anticipatory pleasure is associated with disrupted reward prediction and reduced engagement in reward-seeking behaviours. To investigate the role of the dopamine D₁ receptor in anticipatory pleasure, D₁ mutant rats and WT rats performed five experiments. Reward prediction was examined using the anticipatory locomotion experiment and successive negative contrast experiment. It was found that D₁ mutant rats have impaired anticipatory responses to expected reward. However, as the WT rats did not show the expected response to an alteration in reward expectation, it was impossible to assess the role of the D₁ receptor. Together, these findings suggest that the D₁ receptor may be involved in aspects of reward prediction. Reward-seeking behaviour was examined using the social approach experiment, scent marking experiment, and the separation induced vocalization experiment. It was found that the D₁ mutant rats have an impaired ability to engage in social and sexual reward-seeking behaviours, but have relatively normal ability to engage in maternal reward-seeking behaviours. Together, these findings indicate that the D₁ receptor is involved in certain aspects of reward-seeking behaviours. In conclusion, there is compelling evidence that a D₁ receptor dysfunction is a likely contributor to diminished motivation in schizophrenia.