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bioRxiv · 10.1101/2023.06.28.546959

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

Chapp, A. D.·Nwakama, C. A.·Jagtap, P. P.·Phan, C.-M. H.·Thomas, M. J.·Mermelstein, P. G.
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Abstract

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.

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Chapp, A. D., Nwakama, C. A., Jagtap, P. P., Phan, C.-M. H., Thomas, M. J., Mermelstein, P. G.. 2023-06-30. Fundamental Sex Differences in Cocaine-Induced Plasticity of D1- and D2-MSNs in the Mouse Nucleus Accumbens Shell. https://doi.org/10.1101/2023.06.28.546959

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