Sex, Drugs, and Dopamine in This Day and Age: Photoperiod Differentially Impacts Nucleus Accumbens Dopamine Dynamics by Sex and Age

Light signals have long been recognized as having a powerful influence on the structure and function of specific brain systems. Day length, or photoperiod, is associated with affective behaviors, but the underlying neurobiological mechanisms are largely unknown. The mesolimbic dopamine system, which consists of dopamine input to the nucleus accumbens (NAc), plays a critical role in coordinating affective and motivated behaviors. Here, we provide novel findings of how photoperiod affects dopaminergic-signaling dynamics in the NAc. We assess reward circuit dopamine content and signaling dynamics using mass spectrometry and fast-scan cyclic voltammetry (FSCV) in mice maintained in different photoperiods. To determine behavioral consequences of DA signaling we investigate psychostimulant-induced behaviors. We find differential NAc DA content and that summer-like photoperiod enhances dopamine release and uptake in the NAc of female mice, but not in males. Further, we demonstrate that the dopamine transporters are a primary locus of action for sex-specific photoperiod modulation of dopamine signaling dynamics. Lastly, we demonstrate that photoperiod-driven basal differences in dopamine signaling dynamics manifest in observable differences in dopamine-dependent behaviors. Taken together, this work uncovers a potential synaptic basis for sex-linked seasonality of neuropsychiatric disorders. By revealing novel mechanisms regarding circadian light input and neural plasticity, the findings presented here can change conceptualization of the impact on brain and behavior of a pervasive stimulus - environmental light cycles. This work creates an integrated picture of a novel synaptic mechanism that has potential to stimulate a basis for discovery of environmental influence on typical and atypical neural function.