title: Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.
abstract: Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29-38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre-pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [35S]GTPγS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary, THC and stress interact with the developing endocannabinoid system in a sex specific manner during the peri-pubertal period.
authors.affiliation: School of Graduate Studies, SUNY Downstate Medical Center, 450 Clarkson Ave, MSC 41, Brooklyn, 11203, NY, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Silva
authors.affiliation: School of Graduate Studies, SUNY Downstate Medical Center, 450 Clarkson Ave, MSC 41, Brooklyn, 11203, NY, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Black
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Psychiatry and Neuroscience, Hess Center for Science and Medicine Building, 1470 Madison Avenue, New York, NY 11029, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Michaelides
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Psychiatry and Neuroscience, Hess Center for Science and Medicine Building, 1470 Madison Avenue, New York, NY 11029, USA.
authors.forename: Yasmin L
authors.initials: YL
authors.lastname: Hurd
authors.affiliation: School of Graduate Studies, SUNY Downstate Medical Center, 450 Clarkson Ave, MSC 41, Brooklyn, 11203, NY, USA; Department of Physiology and Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Ave, Mail Stop 29, Brooklyn, 11203, NY, USA. Electronic address: diana.dow-edwards@downstate.edu.
authors.forename: Diana
authors.initials: D
authors.lastname: Dow-Edwards
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D000928:Antidepressive Agents / Q000008:administration & dosage; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D003863:Depression; D013759:Dronabinol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D065808:Prepulse Inhibition / Q000187:drug effects; D011605:Psychoses, Substance-Induced; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects*; D013315:Stress, Psychological
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D003345:Corticosterone
keywords: CB1 receptor expression; Corticosterone; Delta-9-tetrahydrocannabinol; Emotionality; Puberty; Sex differences