title: Disruption of peri-adolescent endocannabinoid signaling modulates adult neuroendocrine and behavioral responses to stress in male rats.
abstract: The endocannabinoid (eCB) system is known to regulate neural, endocrine and behavioral responses to stress in adults; however there is little knowledge regarding how this system governs the development and maturation of these responses. Previous work has reported dynamic and time-specific changes in CB1 receptor expression, N-arachidonylethanolamine (AEA) content and fatty acid amide hydrolase (FAAH) activity within corticolimbic structures throughout the peri-adolescent period. To examine whether fluctuations in adolescent eCB activity contribute to the development of adult stress responsivity and emotionality, we treated male Sprague-Dawley rats daily with the CB1R antagonist, AM-251 (5 mg/kg), or vehicle between post-natal days (PND) 35-45. Following this treatment, emotional behavior, HPA axis stress reactivity and habituation to repeated restraint stress, as well as corticolimbic eCB content were examined in adulthood (PND 75). Behaviorally, AM-251-treated males exhibited more active stress-coping behavior in the forced swim test, greater risk assessment behavior in the elevated plus maze and no significant differences in general motor activity. Peri-adolescent AM-251 treatment modified corticosterone habituation to repeated restraint exposure compared to vehicle. Peri-adolescent CB1R antagonism induced moderate changes in adult corticolimbic eCB signaling, with a significant decrease in amygdalar AEA, an increase in hypothalamic AEA and an increase in prefrontal cortical CB1R expression. Together, these data indicate that peri-adolescent endocannabinoid signaling contributes to the maturation of adult neurobehavioral responses to stress.
authors.affiliation: Dept. of Psychology, University of British Columbia, Vancouver, V6T 1Z4, Canada.
authors.forename: Tiffany T-Y
authors.initials: TT
authors.lastname: Lee
authors.affiliation: Hotchkiss Brain Institute, Dept. of Cell Biology and Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
authors.affiliation: Dept. of Pharmacology and Toxicology and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.affiliation: Dept. of Psychology, University of British Columbia, Vancouver, V6T 1Z4, Canada. Electronic address: bgorzalka@psych.ubc.ca.
authors.forename: Boris B
authors.initials: BB
authors.lastname: Gorzalka
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists / Q000633:toxicity*; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D063388:Endocannabinoids / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000633:toxicity*; D011720:Pyrazoles / Q000633:toxicity*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012149:Restraint, Physical; D012309:Risk-Taking; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: 2-AG; AM-251; Adolescence; Anandamide; CB1 receptor; Elevated plus maze; Forced swim test; HPA axis; Stress reactivity