Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell
Background: Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D1 receptor–expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D2 receptor–expressing medium spiny neurons (D2R-MSNs). In females, the effect of cocaine on accum...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-05-01
|
| Series: | Biological Psychiatry Global Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174324000089 |
| _version_ | 1797256313450790912 |
|---|---|
| author | Andrew D. Chapp Chinonso A. Nwakama Pramit P. Jagtap Chau-Mi H. Phan Mark J. Thomas Paul G. Mermelstein |
| author_facet | Andrew D. Chapp Chinonso A. Nwakama Pramit P. Jagtap Chau-Mi H. Phan Mark J. Thomas Paul G. Mermelstein |
| author_sort | Andrew D. Chapp |
| collection | DOAJ |
| description | Background: Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D1 receptor–expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D2 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. |
| first_indexed | 2024-04-24T22:19:46Z |
| format | Article |
| id | doaj.art-fa18c96506214df9aac4862f83a34dad |
| institution | Directory Open Access Journal |
| issn | 2667-1743 |
| language | English |
| last_indexed | 2024-04-24T22:19:46Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj.art-fa18c96506214df9aac4862f83a34dad2024-03-20T06:11:34ZengElsevierBiological Psychiatry Global Open Science2667-17432024-05-0143100295Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens ShellAndrew D. Chapp0Chinonso A. Nwakama1Pramit P. Jagtap2Chau-Mi H. Phan3Mark J. Thomas4Paul G. Mermelstein5Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota; Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, MinnesotaDepartment of Neuroscience, University of Minnesota, Minneapolis, Minnesota; Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota; Medical Scientist Training Program, Icahn School of Medicine at Mount Sinai, New York, New YorkDepartment of Neuroscience, University of Minnesota, Minneapolis, MinnesotaDepartment of Neuroscience, University of Minnesota, Minneapolis, MinnesotaDepartment of Neuroscience, University of Minnesota, Minneapolis, Minnesota; Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota; Center for Neural Circuits in Addiction, University of Minnesota, Minneapolis, Minnesota; Address correspondence to Mark J. Thomas, Ph.D.Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota; Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota; Center for Neural Circuits in Addiction, University of Minnesota, Minneapolis, Minnesota; Paul G. Mermelstein, Ph.D.Background: Cocaine-induced plasticity in the nucleus accumbens shell of males occurs primarily in dopamine D1 receptor–expressing medium spiny neurons (D1R-MSNs), with little if any impact on dopamine D2 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.http://www.sciencedirect.com/science/article/pii/S2667174324000089CocaineEstrous cycleExcitabilitymEPSCsNucleus accumbens shellSex differences |
| spellingShingle | Andrew D. Chapp Chinonso A. Nwakama Pramit P. Jagtap Chau-Mi H. Phan Mark J. Thomas Paul G. Mermelstein Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell Biological Psychiatry Global Open Science Cocaine Estrous cycle Excitability mEPSCs Nucleus accumbens shell Sex differences |
| title | Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell |
| title_full | Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell |
| title_fullStr | Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell |
| title_full_unstemmed | Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell |
| title_short | Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell |
| title_sort | fundamental sex differences in cocaine induced plasticity of dopamine d1 receptor and d2 receptor expressing medium spiny neurons in the mouse nucleus accumbens shell |
| topic | Cocaine Estrous cycle Excitability mEPSCs Nucleus accumbens shell Sex differences |
| url | http://www.sciencedirect.com/science/article/pii/S2667174324000089 |
| work_keys_str_mv | AT andrewdchapp fundamentalsexdifferencesincocaineinducedplasticityofdopamined1receptorandd2receptorexpressingmediumspinyneuronsinthemousenucleusaccumbensshell AT chinonsoanwakama fundamentalsexdifferencesincocaineinducedplasticityofdopamined1receptorandd2receptorexpressingmediumspinyneuronsinthemousenucleusaccumbensshell AT pramitpjagtap fundamentalsexdifferencesincocaineinducedplasticityofdopamined1receptorandd2receptorexpressingmediumspinyneuronsinthemousenucleusaccumbensshell AT chaumihphan fundamentalsexdifferencesincocaineinducedplasticityofdopamined1receptorandd2receptorexpressingmediumspinyneuronsinthemousenucleusaccumbensshell AT markjthomas fundamentalsexdifferencesincocaineinducedplasticityofdopamined1receptorandd2receptorexpressingmediumspinyneuronsinthemousenucleusaccumbensshell AT paulgmermelstein fundamentalsexdifferencesincocaineinducedplasticityofdopamined1receptorandd2receptorexpressingmediumspinyneuronsinthemousenucleusaccumbensshell |