The research in the present in the present proposal examines the effect of delta-9-tetrahydrocannabinol (THC) on the neuroendocrine system of the female. The proposed experiments will extend earlier studies on the ability of THC to suppress LH/FSH secretion by examining the potential sites and mechanisms of THC action within the central nervous system (CNS). Using a rat animal model, specific studies were designed to identify those hypothalamic and suprahypothalamic sites at which THC may at to inhibit basal and stimulated LH and FSH release by direct administration of a wide dose range of THC into suspected brain regions. Both the preovulatory release of LH/FSH and ovulation in gonad-intact rats and the episodic pattern of gonadotropin secretion in the ovariectomized animal will be determined. In the second part of the proposal, the neural mechanisms which will potentially mediators of THC-induced inhibition of episodic LH secretion will be assessedutilizing the ovariectomized rat treated with THC intravenoulsty. First, the effect of THC on pulsatile GnRH secretion is responsible for THC-induced suppression of episodic LH release. Secondly, the role of specific neurotransmitter systems implicated in the regulation of pulsatile LH secretion as potential mediators of THC-induced inhibition of episodic LH release will be investigated by to use of neurotransmitter synthesis inhiborots and specific receptor blockers. The role of CNS opioid receptor mechanisms in THC-induced inhibition of pulsatile LH release will be assessed by the use of an opiate receptor blocker, naloxone. Finally, the possible involvement of prostaglands in the ability of THC to suppress LH release will be examined. The results of these experiments will increase our understanding of the brain site(s) through which THC acts to suppress pituitary function and lead to identification of the mechanism(s) by which THC alters pituitary hormone secretion. Thus, this proposal should provide much needed information in an area of great societal concern.
