title: Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.
abstract: This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we and others have shown for chronic administration during adolescence.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA, United States; Alcohol and Drug Abuse Center of Excellence, LSU Health Sciences Center, New Orleans, LA, United States. Electronic address: pwinsa@lsuhsc.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Winsauer
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA, United States.
authors.forename: Jessie L
authors.initials: JL
authors.lastname: Sutton
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D020318:Rats, Long-Evans; D012965:Sodium Chloride / Q000008:administration & dosage; D014599:Uterus / Q000187:drug effects
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012965:Sodium Chloride; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol
keywords: Behavior; Learning; Ovariectomy; Rat; Young adults; ∆(9)-tetrahydrocannabinol