The proposed research continues studies on the effects of delta-9-tetrahydrocannabinol (THC) on reproductive endocrine function in the female. The project utilizes the rat model to continue efforts to identify and characterize THC-related disturbances in the neuroendocrine regulation of female reproduction with the long-term objective of identifying the brain site or sites through which THC acts to suppress pituitary function. Identification of a site of action coupled to a measurable endocrine effect should facilitate eventual identification of the mechanism whereby THC alters pituitary hormone secretion. Enhanced understanding of THC action would contribute to an evaluation of the potential impact of marihuana use by humans during the reproductive years. The current studies will extend previous work on THC-induced inhibition of prolactin and LH secretion in more anatomically and mechanistically focused fashions. Localized electrolytic lesions will be utilized to determine if the functional presence of the medial preoptic area or the suprachiasmatic nuclei is required for THC to exert an inhibitory effect on basal or stimulated prolactin secretion. Complete deafferentation of the medial basal hypothalamus will be combined with pharmacologic manipulations of neutrotransmitter systems to evaluate the potential involvement of selected neurotransmitters in the inhibition of episodic LH release by THC. Standard methods of stereotaxic microsurgical deafferentation and brain lesioning will be applied to cyclic female rats which subsequently will be ovariectomized and treated intravenously with THC. Serial blood samples will be obtained from individual alert and unrestrained animals via indwelling atrial cannulae for serum hormone level determinations by radioimmunoassay. The proposed studies also will extend the previous observation of delayed sexual maturation after prepubertal THC treatment by determining if prepubertal treatment with THC is associated with circulating hormone changes which might contribute to the maturational delay and by determining whether there are functional sequelae to the prepubertal treatment and maturational delay in terms of disordered ovarian cyclicity or ovulation.
