Sex differences in behavioral responding and dopamine release during Pavlovian learning

Learning associations between cues and rewards requires the mesolimbic dopamine system. The dopamine response to cues signals differences in reward value in well-trained animals. However, these value-related dopamine responses are absent during early training sessions when cues signal differences in the reward rate. These findings suggest cue-evoked dopamine release conveys differences between outcomes only after extensive training, though it is unclear if this is unique to when cues signal differences in reward rate, or if this is also evident when cues signal differences in other value-related parameters such as reward size. To address this, we utilized a Pavlovian conditioning task in which one audio cue was associated with a small reward (one pellet) and another audio cue was associated with a large reward (three pellets). We performed fast-scan cyclic voltammetry to record changes in dopamine release in the nucleus accumbens of male and female rats throughout learning. While female rats exhibited higher levels of conditioned responding, a faster latency to respond, and elevated post-reward head entries relative to male rats, there were no sex differences in the dopamine response to cues. Multiple training sessions were required before cue-evoked dopamine release signaled differences in reward size. Reward-evoked dopamine release scaled with reward size, though females displayed lower reward-evoked dopamine responses relative to males. Conditioned responding related to the decrease in the peak reward-evoked dopamine response and not to cue-evoked dopamine release. Collectively these data illustrate sex differences in behavioral responding as well as in reward-evoked dopamine release during Pavlovian learning.