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Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.

Peter J Winsauer, Jill M Daniel, Catalin M Filipeanu, Stuart T Leonard, Jerielle L Hulst, Shaefali P Rodgers, Caroline L Lassen-Greene, Jessie L Sutton

Addiction Biology January 2011 DOI: 10.1111/j.1369-1600.2010.00227.x (opens in new tab)

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AI-extracted from the abstract
Characteristics Controlled experimental animal study Peer reviewed
Population Female rats; gonadally intact or ovariectomized, treated during adolescence and tested as adults
Intervention Δ⁹-THC
Dose 5.6 mg/kg daily during adolescence; 0.56-10 mg/kg during adulthood
Duration 40 daily injections during adolescence, with adult re-administration and testing
Topics Cannabis
Key findings Chronic adolescent Δ⁹-THC administration in female rats produced long-term effects on operant learning and performance and on the cannabinoid system that depended on the presence of ovarian hormones. Rats exposed to adolescent THC, ovariectomy, or both were less sensitive to THC's rate-decreasing effects and more sensitive to its error-increasing effects as adults than intact saline-treated controls. CB-1 receptor levels in hippocampus and striatum were persistently altered in a region- and hormone-dependent manner.

Abstract

Abuse of Δ⁹-THC by females during adolescence may produce long-term deficits in complex behavioral processes such as learning, and these deficits may be affected by the presence of ovarian hormones. To assess this possibility, 40 injections of saline or 5.6 mg/kg of Δ⁹-THC were administered i.p. daily during adolescence to gonadally intact or ovariectomized (OVX) female rats, yielding four treatment groups (intact/saline, intact/THC, OVX/saline, and OVX/ THC). Δ⁹-THC (0.56-10 mg/kg) was then re-administered to each of the four groups during adulthood to examine their sensitivity to its disruptive effects. The behavioral task required adult subjects to both learn (acquisition component) different response sequences and repeat a known response sequence (performance component) daily. During baseline (no injection) and control (saline injection) sessions, OVX subjects had significantly higher response rates and lower percentages of error in both behavioral components than the intact groups irrespective of saline or Δ⁹-THC administration during adolescence; the intact group that received Δ⁹-THC had the lowest response rates in each component. Upon re-administration of Δ⁹-THC, the groups that received adolescent ovariectomy alone, adolescent Δ⁹-THC administration alone, or both treatments were found to be less sensitive to the rate-decreasing effects, and more sensitive to the error-increasing effects of Δ⁹-THC than the control group (i.e. intact subjects that received saline during adolescence). Neurochemical analyses of the brains from each adolescent-treated group indicated that there were also persistent effects on cannabinoid type-1 (CB-1) receptor levels in the hippocampus and striatum that depended on the brain region and the presence of ovarian hormones. In addition, autoradiographic analyses of the brains from adolescent-treated, but behaviorally naïve, subjects indicated that ovariectomy and Δ⁹-THC administration produced effects on receptor coupling in some of the same brain regions. In summary, chronic administration of Δ⁹-THC during adolescence in female rats produced long-term effects on operant learning and performance tasks and on the cannabinoid system that were mediated by the presence of ovarian hormones, and that altered their sensitivity to Δ⁹-THC as adults.

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