REDUCED CACNA1C EXPRESSION PRODUCES ANHEDONIC REACTIONS TO PALATABLE SUCROSE IN RATS: NO INTERACTIONS WITH JUVENILE OR ADULT STRESS

Abstract

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Cav1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia, bipolar disorder, and major depression. Here we investigated the impact of mutations of one copy of Cacna1c on rats hedonic responses to palatable sucrose (assessed using the analysis of consumption microstructure). In addition, we also investigated the effects of combining either juvenile or adult stress with the manipulation of Cacna1c. Across three experiments Cacna1c+/- rats displayed attenuated hedonic reactions to sucrose compared to WT littermate controls, despite the Cacna1c+/- rats retaining sensitivity to sucrose concentration in terms of the amount of consumption. Unexpectedly, juvenile stress enhanced rather than reduced hedonic reactions to sucrose, while adult stress did not have clear hedonic effects. The effects of Cacna1c manipulation did not interact with either juvenile or adult stress. The fact that Cacna1c+/- rats display a clear analogue of anhedonia - a reduction in the positive hedonic reactions normally elicited by highly palatable sucrose - a symptom observed transdiagnostically across psychiatric disorders linked to CACNA1C, suggests this model may play a valuable role in the translational fiinvestigation of anhedonia.