Frye C A, Vongher J M
Neuroscience Program, Connecticut College, New London, USA.
Behav Brain Res. 1999 Aug;103(1):23-34. doi: 10.1016/s0166-4328(99)00020-0.
In hamsters, progesterone (P) in the hypothalamus and ventral tegmental area (VTA) is necessary for receptivity; in rats, hypothalamic P induces receptivity and midbrain P further enhances it. How P exerts its effects in the VTA on lordosis is of interest because few estrogen-induced P receptors (PRs) have been identified there. Sexual receptivity of rats and hamsters is enhanced when P's actions in the VTA are restricted to the membrane and when the gamma-aminobutyric acid (GABA)A agonist, muscimol, is infused into the VTA, but attenuated with infusions of the GABA(A) antagonist, bicuculline. The dopamine (DA) agonist. SKF38393, rapidly enhances receptivity when infused intravenously; this effect can be blocked by both DA receptor (DR) and PR antagonists. This study investigated the importance of PRs, glutamic acid decarboxylase (GAD), the enzyme responsible for GABA production, GABA(A) receptors (GBRs), and DRs in the VTA of cycling rats and hamsters for the expression of lordosis. Proestrous and diestrous animals implanted with bilateral VTA cannulae were pre-tested for receptivity, infused with either an antagonist (RU38486 (20 microg), bicuculline (100 ng), SCH23390 (100 ng)), anti-sense oligonucleotide (against PR (250 ng), GAD (500 ng), D1 (500 ng), D5 (250 ng)), or control infusions to each cannulae and re-tested. Vehicle and scrambled oligonucleotides were infused as controls and elicited similar effects. Antagonists of GBRs and DRs significantly reduced lordosis on post-tests compared to the PR antagonist and control conditions in rats and hamsters. Lordosis was significantly reduced, compared to controls, only by anti-sense oligonucleotides for GAD and D1- and D5-DR subtypes. These data suggest that in the VTA GABAergic and dopaminergic neurons may be more important in the mediation of sexual receptivity than neurons containing intracellular PRs.
在仓鼠中，下丘脑和腹侧被盖区（VTA）中的孕酮（P）是接受性所必需的；在大鼠中，下丘脑的P诱导接受性，中脑的P进一步增强接受性。P如何在VTA中对脊柱前凸发挥作用备受关注，因为在那里几乎没有发现雌激素诱导的孕酮受体（PRs）。当P在VTA中的作用局限于细胞膜时，以及当γ-氨基丁酸（GABA）A激动剂蝇蕈醇注入VTA时，大鼠和仓鼠的性接受性增强，但注入GABA（A）拮抗剂荷包牡丹碱时则减弱。多巴胺（DA）激动剂SKF38393静脉注射时能迅速增强接受性；这种效应可被DA受体（DR）拮抗剂和PR拮抗剂阻断。本研究调查了在发情周期的大鼠和仓鼠的VTA中，PRs、谷氨酸脱羧酶（GAD，负责GABA产生的酶）、GABA（A）受体（GBRs）和DRs对脊柱前凸表达的重要性。给植入双侧VTA套管的动情前期和动情间期动物进行接受性预测试，然后向每个套管注入拮抗剂（RU38486（20微克）、荷包牡丹碱（100纳克）、SCH23390（100纳克））、反义寡核苷酸（针对PR（250纳克）、GAD（500纳克）、D1（500纳克）、D5（250纳克））或对照溶液，之后再次进行测试。注入载体和乱序寡核苷酸作为对照，产生了相似的效果。与PR拮抗剂和对照条件相比，GBRs和DRs拮抗剂在大鼠和仓鼠的后测试中显著降低了脊柱前凸。与对照组相比，只有针对GAD以及D1和D5 - DR亚型的反义寡核苷酸显著降低了脊柱前凸。这些数据表明，在VTA中，GABA能和多巴胺能神经元在介导性接受性方面可能比含有细胞内PRs的神经元更重要。
