NEUROENDOCRINE MECHANISMS OF CANNABINOID ACTION

本提案中的研究审查了 δ-9-四氢大麻酚（THC）对神经内分泌的影响 女性的系统。 拟议中的实验将提前 THC抑制LH/FSH分泌的能力的研究， 研究THC作用的潜在部位和机制， 中枢神经系统（CNS）。 使用大鼠动物模型， 设计了特定的研究来识别那些下丘脑和 下丘脑上部位，THC可能在抑制基础和 通过直接给予广泛的刺激LH和FSH释放 四氢大麻酚的剂量范围 两者 排卵前LH/FSH释放与性腺完整大鼠排卵 和促性腺激素分泌的偶发模式， 将确定卵巢切除动物。 第二部分 这个提议，神经机制， THC诱导的LH分泌抑制的介质将 用四氢大麻酚治疗卵巢切除大鼠， 静脉注射 首先，THC对脉动GnRH的影响 分泌是负责THC诱导的抑制发作性 LH释放 第二，特定神经递质的作用 系统参与调节脉动LH分泌， THC诱导的发作性LH抑制的潜在介质 将通过使用神经递质来研究释放 合成异硼酸酯和特异性受体阻断剂。 的作用 四氢大麻酚抑制脑缺血的中枢阿片受体机制 脉冲式LH释放将通过使用阿片类药物进行评估 受体阻断剂纳洛酮。 最后，可能涉及 THC抑制LH释放的能力将是 考察 这些实验的结果将增加我们的 了解THC作用的大脑部位， 抑制垂体功能，并导致识别 THC改变垂体激素分泌的机制。 因此，这项建议应提供急需的信息， 社会高度关注的领域。

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.