首页 | 本学科首页   官方微博 | 高级检索  
     


Sex,drugs, and adult neurogenesis: Sex‐dependent effects of escalating adolescent cannabinoid exposure on adult hippocampal neurogenesis,stress reactivity,and amphetamine sensitization
Authors:Tiffany T.‐Y. Lee  Steven R. Wainwright  Matthew N. Hill  Liisa A.M. Galea  Boris B. Gorzalka
Affiliation:1. Department of PsychologyUniversity of British Columbia, Vancouver, BC, Canada;2. Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada;3. Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada;4. Brain Research Centre, University of British Columbia, Vancouver, BC, Canada
Abstract:Cannabinoid exposure during adolescence has adverse effects on neuroplasticity, emotional behavior, cognition, and reward sensitivity in adult rats. We investigated whether escalating doses of the cannabinoid receptor 1 (CB1R) agonist, HU‐210, in adolescence would affect adult hippocampal neurogenesis and behavioral processes putatively modulated by hippocampal neurogenesis, in adult male and female Sprague‐Dawley rats. Escalating doses of HU‐210 (25, 50, and 100 µg/kg), or vehicle were administered from postnatal day (PND) 35 to 46. Animals were left undisturbed until PND 70, when they were treated with 5‐bromo‐2‐deoxyuridine (BrdU; 200 mg/kg) and perfused 21 days later to examine density of BrdU‐ir and BrdU/NeuN cells in the dentate gyrus. In another cohort, hypothalamic‐pituitary‐adrenal (HPA) axis reactivity to an acute restraint stress (30 min; PND 75) and behavioral sensitization to d‐amphetamine sulfate (1‐2 mg/kg; PND 105‐134) were assessed in adulthood. Adolescent HU‐210 administration suppressed the density of BrdU‐ir cells in the dentate gyrus in adult male, but not adult female rats. Adolescent HU‐210 administration also induced significantly higher peak corticosterone levels and reminiscent of the changes in neurogenesis, this effect was more pronounced in adult males than females. However, adolescent cannabinoid treatment resulted in significantly higher stereotypy scores in adult female, but not male, rats. Thus, adolescent CB1R activation suppressed hippocampal neurogenesis and increased stress responsivity in adult males, but not females, and enhanced amphetamine sensitization in adult female, but not male, rats. Taken together, increased CB1R activation during adolescence results in sex‐dependent, long‐term, changes to hippocampal structure and function, an effect that may shed light on differing vulnerabilities to developing disorders following adolescent cannabinoid exposure, based on sex. © 2013 Wiley Periodicals, Inc.
Keywords:sex difference  CB1 receptor  survival  periadolescent  HPA axis
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号