Crystallin Mu in Medial Amygdala Mediates the Effect of Social Experience on Cocaine Seeking in Males but Not in Females

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dc.contributor.authorWalker, Deena M.en
dc.contributor.authorZhou, Xianxiaoen
dc.contributor.authorCunningham, Ashley M.en
dc.contributor.authorRamakrishnan, Aarthien
dc.contributor.authorCates, Hannah M.en
dc.contributor.authorLardner, Casey K.en
dc.contributor.authorPena, Catherine J.en
dc.contributor.authorBagot, Rosemary C.en
dc.contributor.authorIssler, Ornaen
dc.contributor.authorvan der Zee, Yentlen
dc.contributor.authorLipschultz, Andrew P.en
dc.contributor.authorGodino, Arthuren
dc.contributor.authorBrowne, Caleb J.en
dc.contributor.authorHodes, Georgia E.en
dc.contributor.authorParise, Eric M.en
dc.contributor.authorTorres-Berrio, Angelicaen
dc.contributor.authorKennedy, Pamela J.en
dc.contributor.authorShen, Lien
dc.contributor.authorZhang, Binen
dc.contributor.authorNestler, Eric J.en
dc.date.accessioned2024-01-22T17:40:56Zen
dc.date.available2024-01-22T17:40:56Zen
dc.date.issued2022-06-30en
dc.description.abstractBackground: Social experiences influence susceptibility to substance use disorder. The adolescent period is associated with the development of social reward and is exceptionally sensitive to disruptions to reward-associated behaviors by social experiences. Social isolation (SI) during adolescence alters anxiety- and reward-related behaviors in adult males, but little is known about females. The medial amygdala (meA) is a likely candidate for the modulation of social influence on drug reward because it regulates social reward, develops during adolescence, and is sensitive to social stress. However, little is known regarding how the meA responds to drugs of abuse. Methods: We used adolescent SI coupled with RNA sequencing to better understand the molecular mechanisms underlying meA regulation of social influence on reward. Results: We show that SI in adolescence, a well-established preclinical model for addiction susceptibility, enhances preference for cocaine in male but not in female mice and alters cocaine-induced protein and transcriptional profiles within the adult meA particularly in males. To determine whether transcriptional mechanisms within the meA are important for these behavioral effects, we manipulated Crym expression, a sex-specific key driver gene identified through differential gene expression and coexpression network analyses, specifically in meA neurons. Overexpression of Crym, but not another key driver that did not meet our sex-specific criteria, recapitulated the behavioral and transcriptional effects of adolescent SI. Conclusions: These results show that the meA is essential for modulating the sex-specific effects of social experience on drug reward and establish Crym as a critical mediator of sex-specific behavioral and transcriptional plasticity.en
dc.description.versionAccepted versionen
dc.format.extentPages 895-906en
dc.format.extent12 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.biopsych.2022.06.026en
dc.identifier.eissn1873-2402en
dc.identifier.issn0006-3223en
dc.identifier.issue11en
dc.identifier.orcidHodes, Georgia [0000-0002-1551-2178]en
dc.identifier.otherS0006-3223(22)01396-8 (PII)en
dc.identifier.pmid36182529en
dc.identifier.urihttps://hdl.handle.net/10919/117544en
dc.identifier.volume92en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/36182529en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAdolescent social isolationen
dc.subjectAnxietyen
dc.subjectCocaineen
dc.subjectGene coexpression network analysisen
dc.subjectGene expressionen
dc.subjectRNA sequencingen
dc.subject.meshAmygdalaen
dc.subject.meshNeuronsen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshCocaineen
dc.subject.meshRewarden
dc.subject.meshFemaleen
dc.subject.meshMaleen
dc.subject.meshmu-Crystallinsen
dc.titleCrystallin Mu in Medial Amygdala Mediates the Effect of Social Experience on Cocaine Seeking in Males but Not in Femalesen
dc.title.serialBiological Psychiatryen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2022-06-20en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/School of Neuroscienceen

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