Effects of Estrogen and Cannabinoids on Learning

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DESCRIPTION (provided by applicant) There is growing evidence to indicate that there is an interaction between the biologically active constituent of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), and the ovarian hormone, estrogen, in the central nervous system. However, little information is currently available regarding the functional consequences of this interaction on behavior. Additionally, despite the fact that the behavioral effects of other drugs of abuse are influenced by estrogenic status, the behavioral effects of delta 9-THC in female animal models have not been investigated. The experiments in the proposed study will test the following hypotheses: 1) Estrogen replacement will attenuate the disruptive effects of systemically administered delta 9-THC on overall response rate and percent errors in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance of behavioral chains. 2) Estrogen replacement will differentially affect levels of cannabinoid receptor binding, as measured by quantitative receptor autoradiography, in brain areas implicated in learning and memory and will potentiate decreases in cannabinoid receptor binding induced by chronic administration of delta 9-THC. 3) Estrogen replacement will accelerate the development of delta 9-THC-induced behavioral tolerance in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance of behavioral chains. 4) Estrogen replacement will attenuate the disruptive effects of intrahippocampally-administered delta 9-THC on overall response rate and percent errors in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance of behavioral chains. These results will provide, for the first time, information regarding the interactive effects of estrogen and delta 9-THC on behavior.