Meredith J M, Moffatt C A, Auger A P, Snyder G L, Greengard P, Blaustein J D
Division of Neurotoxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas 72079, USA.
J Neurosci. 1998 Dec 1;18(23):10189-95. doi: 10.1523/JNEUROSCI.18-23-10189.1998.
Vaginal-cervical stimulation induces a number of physiological and behavioral events, including the facilitation of mating behavior. Although the facilitation of one component of mating behavior, lordosis, by vaginal-cervical stimulation does not require the presence of progesterone, it appears to be mediated by neural progestin receptors. Abundant evidence suggests that dopamine may play a role in the neural circuitry activated by vaginal-cervical stimulation, including the mating-induced release of dopamine in progestin receptor-containing areas of the brain, changes in the activational state of progestin receptors because of dopamine D1 receptor stimulation, facilitation of lordosis by D1 receptor stimulation in estradiol-primed rats via progesterone-independent events, and D1 agonist-induced neuronal responses in progestin receptor-containing areas and cells. We tested the hypothesis that vaginal-cervical stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32; Mr = 32,000), a protein phosphorylated predominantly in response to the stimulation of D1 receptors. At 9 d after ovariectomy, female rats were injected subcutaneously with a behaviorally effective dose of estradiol benzoate. At 48 hr later they received vaginal-cervical or control (perineal) stimulation, and they were perfused 1 hr later. Vaginal-cervical stimulation increased the number of cells expressing pDARPP-32 immunoreactivity by 92% in the medial preoptic nucleus, 134% in the caudal ventromedial hypothalamic nucleus, 123% in the posterodorsal medial amygdala, and 103% in the bed nucleus of the stria terminalis. These results suggest that some of the neuronal effects of vaginal-cervical stimulation, and perhaps other social or environmental stimuli, are mediated by phosphorylation of DARPP-32, perhaps via stimulation of D1 receptors, within progestin receptor-containing areas.
阴道 - 宫颈刺激会引发一系列生理和行为反应,包括促进交配行为。尽管阴道 - 宫颈刺激对交配行为的一个组成部分——脊柱前凸的促进作用并不需要孕酮的存在,但这一作用似乎是由神经孕激素受体介导的。大量证据表明,多巴胺可能在由阴道 - 宫颈刺激激活的神经回路中发挥作用,这包括在大脑中含孕激素受体区域交配诱导的多巴胺释放、由于多巴胺D1受体刺激导致的孕激素受体激活状态的变化、在经雌二醇预处理的大鼠中通过非孕酮依赖事件由D1受体刺激促进脊柱前凸,以及D1激动剂在含孕激素受体的区域和细胞中诱导的神经元反应。我们测试了这样一个假设,即阴道 - 宫颈刺激会诱导多巴胺和环磷酸腺苷调节的磷蛋白(DARPP - 32;分子量 = 32,000)的磷酸化,该蛋白主要在对D1受体刺激的反应中发生磷酸化。在卵巢切除术后9天,给雌性大鼠皮下注射行为有效剂量的苯甲酸雌二醇。48小时后,它们接受阴道 - 宫颈或对照(会阴)刺激,1小时后进行灌注。阴道 - 宫颈刺激使内侧视前核中表达pDARPP - 32免疫反应性的细胞数量增加了92%,在尾侧腹内侧下丘脑核中增加了134%,在杏仁核后内侧背核中增加了123%,在终纹床核中增加了103%。这些结果表明,阴道 - 宫颈刺激的一些神经元效应,或许还有其他社会或环境刺激,可能是通过在含孕激素受体区域内DARPP - 32的磷酸化介导的,可能是通过刺激D1受体实现的。