Fundamental Sex Differences in Cocaine-Induced Plasticity of D1- and D2-MSNs in the Mouse Nucleus Accumbens Shell

Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in D1 dopamine receptor expressing neurons (D1-MSNs), with little if any impact on D2 dopamine receptor neurons (D2-MSNs). Using ex vivo whole cell recordings in male and female mice, we observe alterations in D1-MSN excitability across the estrous cycle similar in magnitude to the actions of cocaine in males. Furthermore, cocaine shifts estrous cycle-dependent plasticity from intrinsic excitability changes in D1-MSNs to D2-MSNs. Overall, while there are similar cocaine-induced disparities regarding the relative excitability of D1-MSN versus D2-MSN between the sexes, in males this is mediated through reduced D1-MSN excitability, whereas in females it is due to heightened D2-MSN excitability. ### Competing Interest Statement The authors have declared no competing interest.