Identification of photoperiod as a regulator of dopamine-mediated behavior in female mice.

Photoperiod is the primary environmental cue that regulates changes in behavior across seasons. Previously, we have shown that photoperiod has sex-specific effects on synaptic dopamine dynamics in the nucleus accumbens (NAc). Further, evidence suggests that the dopamine transporter (DAT) is a potential locus of action for the sex-specific effects of photoperiod on NAc dopamine. The NAc is a critical node within the reward circuit that brings motivation to action, and changes to NAc dopamine dynamics at the synapse can result in robust changes in behaviors. Cocaine is a psychostimulant that targets monoamine transporters, including DAT, and generates robust behavioral effects. Thus, using cocaine-mediated behavior, we can determine whether photoperiod impacts DAT function and dopamine physiology. Here, using male and female mice we examined the effect of seasonally relevant photoperiods on DAT function in the NAc and dopamine-dependent behavior. We found that females raised in Short, winter-like photoperiod have blunted cocaine-induced hyperlocomotion. Conversely, females raised in Long, summer-like photoperiod exhibit greater DA release and cocaine-mediated DAT inhibition while we observe decreased sensitivity to cocaine-associated learning. The combined work presented here provides evidence that photoperiod has differential, female-specific effects on NAc DAT function and DAT-mediated behaviors.