Petralia Sandra M, DeBold Joseph F, Frye Cheryl A
Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
Pharmacol Biochem Behav. 2007 Feb;86(2):377-85. doi: 10.1016/j.pbb.2007.01.005. Epub 2007 Jan 13.
Progesterone initiates female sexual behavior of rodents (lordosis) through actions at intracellular progestin receptors in the ventromedial hypothalamus. Progesterone's metabolite, 5alpha-pregnan-3alpha-ol-20-one, mediates the intensity and duration of lordosis through its actions at GABA(A) receptors in the ventral tegmental area. Whether progestins can influence sexual behavior through actions that involve N-methyl-D-aspartate receptors (NMDARs) in the ventromedial hypothalamus and ventral tegmental area was investigated. The current study examines the effect of bilateral ventral tegmental area or ventromedial hypothalamus infusions of the non-competitive NMDAR antagonist (+)-MK-801 hydrogen maleate (MK-801; 0, 20, or 200 ng) on lordosis, motor activity, and NMDA R1 subtype (NMDAR1) immunoreactivity in estradiol benzoate (10 microg)+progesterone (50 microg)- and estradiol benzoate+vehicle primed rats. Compared to vehicle infusions, infusions of MK-801 to the ventral tegmental area facilitated lordosis of estradiol benzoate (10 microg)+progesterone (50 microg)- and estradiol benzoate+vehicle primed rats. Infusions of MK-801 to the ventromedial hypothalamus inhibited lordosis of estradiol benzoate (10 microg)+progesterone (50 microg)- and estradiol benzoate+vehicle primed rats, compared to vehicle. There was no effect of MK-801 infusions to the ventral tegmental area or the ventromedial hypothalamus on motor behavior. Immunocytochemistry for NMDAR1 revealed MK-801 (200 ng) infusions to the ventral tegmental area or ventromedial hypothalamus of estradiol benzoate (10 microg)+progesterone (50 microg)- or estradiol benzoate+vehicle primed rats significantly reduced the number of darkly stained NMDAR1-immunoreactive cells, compared to vehicle infusions. These data suggest NMDARs may be important in the mediation of hormonal actions in both the ventral tegmental area and the ventromedial hypothalamus for sexual receptivity of rodents, but in different ways.
孕酮通过作用于腹内侧下丘脑的细胞内孕激素受体来引发啮齿动物的雌性性行为(脊柱前凸)。孕酮的代谢产物5α-孕烷-3α-醇-20-酮通过其作用于腹侧被盖区的GABAA受体来介导脊柱前凸的强度和持续时间。研究了孕激素是否能通过涉及腹内侧下丘脑和腹侧被盖区的N-甲基-D-天冬氨酸受体(NMDARs)的作用来影响性行为。本研究考察了向双侧腹侧被盖区或腹内侧下丘脑注射非竞争性NMDAR拮抗剂马来酸氢盐(+)-MK-801(MK-801;0、20或200 ng)对苯甲酸雌二醇(10μg)+孕酮(50μg)以及苯甲酸雌二醇+赋形剂预处理大鼠的脊柱前凸、运动活性和NMDA R1亚型(NMDAR1)免疫反应性的影响。与注射赋形剂相比,向腹侧被盖区注射MK-801促进了苯甲酸雌二醇(10μg)+孕酮(50μg)以及苯甲酸雌二醇+赋形剂预处理大鼠的脊柱前凸。与注射赋形剂相比,向腹内侧下丘脑注射MK-801抑制了苯甲酸雌二醇(10μg)+孕酮(50μg)以及苯甲酸雌二醇+赋形剂预处理大鼠的脊柱前凸。向腹侧被盖区或腹内侧下丘脑注射MK-801对运动行为没有影响。NMDAR1免疫细胞化学显示,与注射赋形剂相比,向苯甲酸雌二醇(10μg)+孕酮(50μg)或苯甲酸雌二醇+赋形剂预处理大鼠的腹侧被盖区或腹内侧下丘脑注射MK-801(200 ng)显著减少了深色染色的NMDAR1免疫反应性细胞数量。这些数据表明,NMDARs可能在介导腹侧被盖区和腹内侧下丘脑的激素作用以促进啮齿动物的性接受能力方面很重要,但方式不同。