MECHANISMS OF ORPHANIN'S EFFECTS ON PROLACTIN RELEASE

待检验的假设是孤啡肽FQ（OFQ）参与 在催乳素分泌的生理调节中， 作用机制是在下丘脑水平。具体来说，OFQ抑制 结节漏斗和结节垂体多巴胺能神经元（TIDA）的活性 和THDA）神经元，其对 催乳素分泌此外，OFQ在催乳素中起生理作用 调节并参与哺乳诱导的催乳素增加。的 将使用几种方法在雄性和雌性大鼠中检验假设。 首先，将通过确定 对OFQ给药的神经化学反应。DOPA累积将用作 多巴胺能活性指数和5-羟色氨酸作为 催乳素相关脑内特定区域的肾上腺素能活动 调控二、刺激作用的药理特异性 OFQ对催乳素释放的影响将通过阻断这种反应来证明， Acetyl-RYYRIK-NH2，一种OFQ拮抗剂，已被证明具有拮抗剂 老鼠大脑的活动。第三，双标记免疫细胞化学研究将 确定弓状核中特定的多巴胺能神经元， 受OFQ抑制。酪氨酸羟化酶和c-fos的同时表达 将被审查。最后，研究了孤啡肽在介导哺乳诱导的 泌乳素增加将通过预处理的产后、哺乳期 雌性大鼠在哺乳期之前给予乙酰基-RYYRIK-NH 2。的 哺乳引起的催乳素增加，以及哺乳引起的抑制 TIDA和THDA神经元的激活和多巴胺能神经元的激活，将是 量化。 这项研究的长期目标是了解神经 催乳素释放的调节和催乳素之间的相互作用 在不同的生理状态下释放和抑制因子，如 哺乳期，以及性别差异的调节这种激素。 催乳素具有许多重要的生理作用。它会影响生殖 功能（例如，高泌乳素血症与月经过少相关），以及 催乳素水平受到压力和运动的影响， 生殖周期为了了解生殖障碍或 由于压力造成的疾病，重要的是要了解的性质， 调节催乳素的各种因素之间的联系 分泌物

The hypothesis to be tested is that Orphanin FQ (OFQ) is involved in the physiological regulation of prolactin secretion and that this peptide's mechanism of action is at the hypothalamic level. Specifically, OFQ inhibits the activity of the tuberoinfundibular and tuberohypophyseal dopaminergic (TIDA and THDA, respectively) neurons, which produces a stimulatory effect on prolactin secretion. Furthermore, OFQ plays a physiological role in prolactin regulation and is involved in the suckling-induced prolactin increase. The hypothesis will be tested using several approaches in male and females rats. First, the mechanism of action will be examined by determining the neurochemical response to OFQ administration. DOPA accumulation will be used as index of dopaminergic activity and 5-hydroxytryptophan as an index of serotonergic activity in specific regions of the brain involved in prolactin regulation. Second, pharmacological specificity of the stimulatory effects of OFQ on prolactin release will be demonstrated by blocking this response with Acetyl-RYYRIK-NH2, an OFQ antagonist that has been shown to have antagonist activity in rat brain. Third, double-label immunocyto-chemical studies will determine the specific dopaminergic neurons in the arcuate nucleus that are inhibited by OFQ. Simultaneous expression of tyrosine hydroxylase and c-fos will be examined. Finally, the role of OFQ in mediating the suckling-induced prolactin increase will be determined by pretreated post-partum, lactating female rats with Acetyl-RYYRIK-NH2 prior to a suckling bout. The suckling-induced prolactin increase, as well as the suckling-induced inhibition of TIDA and THDA neurons and activation of serotonergic neurons, will be quantified. The long term objectives of this research are to understand the neural regulation of prolactin release and the interaction between the prolactin releasing and inhibiting factors in different physiological states, such as lactation, as well as gender differences in the regulation of this hormone. Prolactin has many important physiological roles. It can affect reproductive functions (e.g. hyperprolactinemia is associated with oligomenorrhea) and prolactin levels are affected by stress and exercise, which influences reproductive cyclicity. In order to understand reproductive disorders or disorders due to stress, it its important to understand the nature of the connections between the various and numerous factors regulating prolactin secretion.