Effects of ∆⁹-THC on memory in ovariectomized and intact female rats

The effects of marijuana's major psychoactive cannabinoid, ∆⁹-tetrahydrocannibinol (∆⁹-THC), were examined on memory in female rats by training subjects to respond under a repeated acquisition and delayed-performance procedure. During this task, subjects acquired a different 4-response sequence each session, which was then recalled after a delay. Sequence retention was tested following various delays, and quantified by a percent savings measure. Response rate and percent errors were also recorded. Subsequent to training, subjects underwent an ovariectomy (OVX) or sham surgery (intact). The OVX group then underwent implantation of subcutaneous 17β-estradiol capsules while the intact group received chronic administration of 1 mg/kg of the estrogen receptor modifier, tamoxifen. Increasing delays from 1 min to 24 h produced delay-dependent decreases in percent savings in both OVX and intact rats. Acute administration of ∆⁹-THC (0.32-3.2 mg/kg) dose-dependently decreased retention, increased percent errors, and decreased response rate in both groups when the delay was 1 h. However, intact rats showed a significantly lower percent savings than OVX rats at the 0.56-mg/kg dose. Delays of 3 h enhanced the disruptive effects of ∆⁹-THC more in intact than OVX rats; furthermore, implantation of 17β-estradiol attenuated ∆⁹-THC-induced disruptions in OVX rats and significantly increased estradiol levels and uterine weight as compared to intact rats. Although chronic tamoxifen administration did not alter ∆⁹-THC's effects on memory in intact rats, it did significantly decrease response rate. These results demonstrate the capacity of chronic 17β-estradiol for attenuating ∆⁹-THC's acute memory-disrupting effects in OVX female rats.