title: Chronic exposure to Delta9-tetrahydrocannabinol downregulates oxytocin and oxytocin-associated neurophysin in specific brain areas.
abstract: Cannabinoids are widely abused drugs. Our goal was to identify genes modulated by Delta9-tetrahydrocannabinol (Delta9-THC) treatment. We found that chronic administration of Delta9-THC (1.5 mg/kg/day, i.p.; 7 days) to rats, downregulates the expression of oxytocin-neurophysin (OT-NP) mRNA and of OT and oxytocin-associated NP (NPOT) immunoreactivity in nucleus accumbens (NAc) and ventral tegmental area (VTA), brain areas involved in reward and addiction. Real-time PCR revealed a 60% and 53% reduction of OT-NP mRNA in NAc and VTA, respectively, under chronic treatment, while no changes were observed in NAc after 24 h. Immunohistochemistry showed a large decrease in number of OT and NPOT-stained fibers in NAc (by 59% and 52%, respectively) and VTA (by 50% and 56%, respectively). No changes in cell staining were observed in the paraventricular nucleus and supraoptic nucleus. As OT is known to inhibit development of drug tolerance and attenuate withdrawal symptoms, we suggest that OT downregulation could play a role during the establishment of the chronic effects of Delta9-THC.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Butovsky
authors.forename: Ana
authors.initials: A
authors.lastname: Juknat
authors.forename: Judith
authors.initials: J
authors.lastname: Elbaz
authors.forename: Maytal
authors.initials: M
authors.lastname: Shabat-Simon
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Abraham
authors.initials: A
authors.lastname: Zangen
authors.forename: Miriam
authors.initials: M
authors.lastname: Altstein
authors.forename: Zvi
authors.initials: Z
authors.lastname: Vogel
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D013759:Dronabinol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006213:Hallucinogens / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009481:Neurophysins / Q000235:genetics / Q000378:metabolism*; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006213:Hallucinogens; D009481:Neurophysins; D012333:RNA, Messenger; D010121:Oxytocin; D013759:Dronabinol