Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor- and D2 Receptor-Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell

Overview

Journal Biol Psychiatry Glob Open Sci

Date 2024 Mar 27

PMID 38533248

Authors

Andrew D Chapp

Chinonso A Nwakama

Pramit P Jagtap

Chau-Mi H Phan

Mark J Thomas

Paul G Mermelstein

Affiliations

Soon will be listed here.

Abstract

Background: Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D receptor-expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D receptor-expressing medium spiny neurons (D2R-MSNs). In females, the effect of cocaine on accumbens shell D1R- and D2R-MSN neurophysiology has yet to be reported, nor have estrous cycle effects been accounted for.

Methods: We used a 5-day locomotor sensitization paradigm followed by a 10- to 14-day drug-free abstinence period. We then obtained ex vivo whole-cell recordings from fluorescently labeled D1R-MSNs and D2R-MSNs in the nucleus accumbens shell of male and female mice during estrus and diestrus. We examined accumbens shell neuronal excitability as well as miniature excitatory postsynaptic currents (mEPSCs).

Results: In females, we observed alterations in D1R-MSN excitability across the estrous cycle similar in magnitude to the effects of cocaine in males. Furthermore, cocaine shifted estrous cycle-dependent plasticity from intrinsic excitability changes in D1R-MSNs to D2R-MSNs. In males, cocaine treatment produced the anticipated drop in D1R-MSN excitability with no effect on D2R-MSN excitability. Cocaine increased mEPSC frequencies and amplitudes in D2R-MSNs from females in estrus and mEPSC amplitudes of D2R-MSNs from females in diestrus. In males, cocaine increased both D1R- and D2R-MSN mEPSC amplitudes with no effect on mEPSC frequencies.

Conclusions: Overall, while there are similar cocaine-induced disparities regarding the relative excitability of D1R-MSNs versus D2R-MSNs between the sexes, this is mediated through reduced D1R-MSN excitability in males, whereas it is due to heightened D2R-MSN excitability in females.

Citing Articles

Sex differences in mouse infralimbic cortex projections to the nucleus accumbens shell.

Johnson C, Chapp A, Lind E, Thomas M, Mermelstein P Biol Sex Differ. 2023; 14(1):87.

PMID: 38082417 PMC: 10712109. DOI: 10.1186/s13293-023-00570-3.

References

Shanley M, Miura Y, Guevara C, Onoichenco A, Kore R, Ustundag E . Estrous Cycle Mediates Midbrain Neuron Excitability Altering Social Behavior upon Stress. J Neurosci. 2022; 43(5):736-748. PMC: 9899085. DOI: 10.1523/JNEUROSCI.1504-22.2022. View

Kim J, Park B, Lee J, Park S, Kim J . Cell type-specific alterations in the nucleus accumbens by repeated exposures to cocaine. Biol Psychiatry. 2011; 69(11):1026-34. DOI: 10.1016/j.biopsych.2011.01.013. View

Kravitz A, Tye L, Kreitzer A . Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci. 2012; 15(6):816-8. PMC: 3410042. DOI: 10.1038/nn.3100. View

Kourrich S, Thomas M . Similar neurons, opposite adaptations: psychostimulant experience differentially alters firing properties in accumbens core versus shell. J Neurosci. 2009; 29(39):12275-83. PMC: 3307102. DOI: 10.1523/JNEUROSCI.3028-09.2009. View

Mu P, Moyer J, Ishikawa M, Zhang Y, Panksepp J, Sorg B . Exposure to cocaine dynamically regulates the intrinsic membrane excitability of nucleus accumbens neurons. J Neurosci. 2010; 30(10):3689-99. PMC: 2853189. DOI: 10.1523/JNEUROSCI.4063-09.2010. View

Mews P, Cunningham A, Scarpa J, Ramakrishnan A, Hicks E, Bolnick S . Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models. Sci Adv. 2023; 9(6):eadd8946. PMC: 9916993. DOI: 10.1126/sciadv.add8946. View

Lobo M, Covington 3rd H, Chaudhury D, Friedman A, Sun H, Damez-Werno D . Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science. 2010; 330(6002):385-90. PMC: 3011229. DOI: 10.1126/science.1188472. View

Lefevre E, Gauthier E, Bystrom L, Scheunemann J, Rothwell P . Differential Patterns of Synaptic Plasticity in the Nucleus Accumbens Caused by Continuous and Interrupted Morphine Exposure. J Neurosci. 2022; 43(2):308-318. PMC: 9838694. DOI: 10.1523/JNEUROSCI.0595-22.2022. View

Yeh S, Estill M, Lardner C, Browne C, Minier-Toribio A, Futamura R . Cell Type-Specific Whole-Genome Landscape of ΔFOSB Binding in the Nucleus Accumbens After Chronic Cocaine Exposure. Biol Psychiatry. 2023; 94(5):367-377. PMC: 10314970. DOI: 10.1016/j.biopsych.2022.12.021. View

10.

Chapp A, Nwakama C, Collins A, Mermelstein P, Thomas M . Physiological acetic acid concentrations from ethanol metabolism stimulate accumbens shell medium spiny neurons via NMDAR activation in a sex-dependent manner. Neuropsychopharmacology. 2023; 49(5):885-892. PMC: 10948831. DOI: 10.1038/s41386-023-01752-8. View

11.

He Y, Wang J, Li K, Wang Y, Freyberg Z, Dong Y . Membrane excitability of nucleus accumbens neurons gates the incubation of cocaine craving. Neuropsychopharmacology. 2023; 48(9):1318-1327. PMC: 10354025. DOI: 10.1038/s41386-023-01580-w. View

12.

Calipari E, Juarez B, Morel C, Walker D, Cahill M, Ribeiro E . Dopaminergic dynamics underlying sex-specific cocaine reward. Nat Commun. 2017; 8:13877. PMC: 5234081. DOI: 10.1038/ncomms13877. View

13.

Pascoli V, Turiault M, Luscher C . Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour. Nature. 2011; 481(7379):71-5. DOI: 10.1038/nature10709. View

14.

Thomas M, Beurrier C, Bonci A, Malenka R . Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci. 2001; 4(12):1217-23. DOI: 10.1038/nn757. View

15.

Kourrich S, Rothwell P, Klug J, Thomas M . Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens. J Neurosci. 2007; 27(30):7921-8. PMC: 6672735. DOI: 10.1523/JNEUROSCI.1859-07.2007. View

16.

Dobi A, Seabold G, Christensen C, Bock R, Alvarez V . Cocaine-induced plasticity in the nucleus accumbens is cell specific and develops without prolonged withdrawal. J Neurosci. 2011; 31(5):1895-904. PMC: 3040105. DOI: 10.1523/JNEUROSCI.5375-10.2011. View

17.

Godino A, Salery M, Durand-de Cuttoli R, Estill M, Holt L, Futamura R . Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards. Neuron. 2023; 111(9):1453-1467.e7. PMC: 10164098. DOI: 10.1016/j.neuron.2023.02.013. View

18.

Renteria R, Maier E, Buske T, Morrisett R . Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure. Neuropharmacology. 2016; 112(Pt A):164-171. PMC: 5755972. DOI: 10.1016/j.neuropharm.2016.03.004. View

19.

Byers S, Wiles M, Dunn S, Taft R . Mouse estrous cycle identification tool and images. PLoS One. 2012; 7(4):e35538. PMC: 3325956. DOI: 10.1371/journal.pone.0035538. View

20.

Chapp A, Nwakama C, Thomas M, Meisel R, Mermelstein P . Sex Differences in Cocaine Sensitization Vary by Mouse Strain. Neuroendocrinology. 2023; 113(11):1167-1176. PMC: 11645863. DOI: 10.1159/000530591. View