Ruth H Asch, Krista Fowles, Robert H Pietrzak, Jane R Taylor, Irina Esterlis
{"title":"mGlu5受体可用性作为PTSD易感性的预测因子:一项雄性和雌性大鼠FPEB和PET研究[18F]。","authors":"Ruth H Asch, Krista Fowles, Robert H Pietrzak, Jane R Taylor, Irina Esterlis","doi":"10.1177/24705470231215001","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Females are twice as likely to experience post-traumatic stress disorder (PTSD) than males, yet specific factors contributing to this greater risk are not fully understood. Our clinical and recent preclinical findings suggest a role for the metabotropic glutamate receptor 5 (mGlu5) in PTSD and differential involvement between males and females.</p><p><strong>Methods: </strong>Here, we further investigate whether mGlu5 receptor availability may contribute to individual and sex differences in PTSD susceptibility by quantifying receptor availability using the mGlu5 receptor-specific radiotracer, [<sup>18</sup>F]FPEB, and positron emission tomography in male (n = 16) and female (n = 16) rats before and after traumatic footshock exposure (FE) and assessment of stress-enhanced fear learning (SEFL) susceptibility, as compared with no-shock controls (CON; n = 7 male; n = 8 female).</p><p><strong>Results: </strong>Overall, FE rats displayed greater fear generalization as compared with CON (<i>p </i>< .001). Further, greater mGlu5 receptor availability at baseline (<i>p </i>= .003) and post-test (<i>p </i>= .005) was significantly associated with expression of the SEFL phenotype. Notably, FE female rats displayed a shift to more passive coping (ie, freezing), and displayed greater SEFL susceptibility (<i>p </i>= .01), and had lower baseline mGlu5 availability (<i>p </i>= .03) relative to their FE male rat counterparts.</p><p><strong>Conclusion: </strong>Results are consistent with clinical findings of higher mGlu5 receptor availability in PTSD, and add to growing evidence implicating these receptors in the pathophysiology of PTSD and sex-differences in susceptibility for this disorder.</p>","PeriodicalId":52315,"journal":{"name":"Chronic Stress","volume":"7 ","pages":"24705470231215001"},"PeriodicalIF":0.0000,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666551/pdf/","citationCount":"0","resultStr":"{\"title\":\"Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [<sup>18</sup>F]FPEB and PET Study in Male and Female Rats.\",\"authors\":\"Ruth H Asch, Krista Fowles, Robert H Pietrzak, Jane R Taylor, Irina Esterlis\",\"doi\":\"10.1177/24705470231215001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Females are twice as likely to experience post-traumatic stress disorder (PTSD) than males, yet specific factors contributing to this greater risk are not fully understood. Our clinical and recent preclinical findings suggest a role for the metabotropic glutamate receptor 5 (mGlu5) in PTSD and differential involvement between males and females.</p><p><strong>Methods: </strong>Here, we further investigate whether mGlu5 receptor availability may contribute to individual and sex differences in PTSD susceptibility by quantifying receptor availability using the mGlu5 receptor-specific radiotracer, [<sup>18</sup>F]FPEB, and positron emission tomography in male (n = 16) and female (n = 16) rats before and after traumatic footshock exposure (FE) and assessment of stress-enhanced fear learning (SEFL) susceptibility, as compared with no-shock controls (CON; n = 7 male; n = 8 female).</p><p><strong>Results: </strong>Overall, FE rats displayed greater fear generalization as compared with CON (<i>p </i>< .001). Further, greater mGlu5 receptor availability at baseline (<i>p </i>= .003) and post-test (<i>p </i>= .005) was significantly associated with expression of the SEFL phenotype. Notably, FE female rats displayed a shift to more passive coping (ie, freezing), and displayed greater SEFL susceptibility (<i>p </i>= .01), and had lower baseline mGlu5 availability (<i>p </i>= .03) relative to their FE male rat counterparts.</p><p><strong>Conclusion: </strong>Results are consistent with clinical findings of higher mGlu5 receptor availability in PTSD, and add to growing evidence implicating these receptors in the pathophysiology of PTSD and sex-differences in susceptibility for this disorder.</p>\",\"PeriodicalId\":52315,\"journal\":{\"name\":\"Chronic Stress\",\"volume\":\"7 \",\"pages\":\"24705470231215001\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666551/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chronic Stress\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/24705470231215001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"Psychology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chronic Stress","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/24705470231215001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Psychology","Score":null,"Total":0}
Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats.
Background: Females are twice as likely to experience post-traumatic stress disorder (PTSD) than males, yet specific factors contributing to this greater risk are not fully understood. Our clinical and recent preclinical findings suggest a role for the metabotropic glutamate receptor 5 (mGlu5) in PTSD and differential involvement between males and females.
Methods: Here, we further investigate whether mGlu5 receptor availability may contribute to individual and sex differences in PTSD susceptibility by quantifying receptor availability using the mGlu5 receptor-specific radiotracer, [18F]FPEB, and positron emission tomography in male (n = 16) and female (n = 16) rats before and after traumatic footshock exposure (FE) and assessment of stress-enhanced fear learning (SEFL) susceptibility, as compared with no-shock controls (CON; n = 7 male; n = 8 female).
Results: Overall, FE rats displayed greater fear generalization as compared with CON (p < .001). Further, greater mGlu5 receptor availability at baseline (p = .003) and post-test (p = .005) was significantly associated with expression of the SEFL phenotype. Notably, FE female rats displayed a shift to more passive coping (ie, freezing), and displayed greater SEFL susceptibility (p = .01), and had lower baseline mGlu5 availability (p = .03) relative to their FE male rat counterparts.
Conclusion: Results are consistent with clinical findings of higher mGlu5 receptor availability in PTSD, and add to growing evidence implicating these receptors in the pathophysiology of PTSD and sex-differences in susceptibility for this disorder.
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