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

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

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

Content Provider	PubMed Central
Author	Winsauer, Peter J. Daniel, Jill M. Filipeanu, Catalin M. Leonard, Stuart T. Hulst, Jerielle L. Rodgers, Shaefali P. Lassen-greene, Caroline L. Sutton, Jessie L.
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 4 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 4 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, ovariectomized 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.
Starting Page	64
File Format	PDF
ISSN	13691600
e-ISSN	13691600
Journal	Addiction biology
Issue Number	1
Volume Number	16
Language	English
Publisher Date	2011-01-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology Psychiatry and Mental Health

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