NEUROENDOCRINE MECHANISMS OF CANNABINOID ACTION

本提案中目前的研究考察了 β-9-四氢大麻酚对神经内分泌的影响 女性的制度。拟议的实验将更早地延长 促性腺激素释放激素抑制黄体生成素/卵泡刺激素分泌能力的研究 审查THC的潜在作用地点和机制 中枢神经系统(CNS)。使用一种大鼠动物模型， 专门的研究旨在确定这些下丘脑和 下丘脑以上部位，THC可能位于抑制基础和 直接给药促进促黄体生成素和促性腺激素释放 THC进入可疑脑区的剂量范围。这两个 性腺完整大鼠排卵前促黄体生成素/卵泡刺激素的释放与排卵 和促性腺激素分泌的间歇性模式 卵巢切除的动物将被确定。在第二部分中 这项提议，神经机制，可能会 THC诱导的阵发性黄体生成素分泌抑制的介体将 THC治疗去卵巢大鼠的实验研究 静脉注射。第一，THC对搏动性促性腺激素释放激素的影响 分泌是THC诱导的发作抑制的原因 促黄体生成素释放。第二，特定神经递质的作用 与调节脉动性促黄体生成素分泌有关的系统 四氢呋喃抑制发作性黄体生成素的潜在介导物 释放将通过使用神经递质进行研究 合成抑制剂和特异性受体阻滞剂。的作用 中枢阿片受体在四氢呋喃抑制作用中的作用机制 黄体生成素的脉动性释放将通过使用阿片剂进行评估 受体阻滞剂纳洛酮。最后，可能参与的 前列腺素具有抑制THC释放黄体生成素的能力 检查过了。这些实验的结果将增加我们的 对大脑部位(S)的理解，THC通过其作用于 抑制垂体功能，并导致鉴定 改变脑下垂体激素分泌的机制(S)。 因此，这项提案应该在一份 这是一个备受社会关注的领域。

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.