Converse Alexander K, Aubert Yves, Allers Kelly A, Sommer Bernd, Abbott David H
Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
J Sex Med. 2015 Dec;12(12):2256-66. doi: 10.1111/jsm.13068. Epub 2015 Dec 4.
Female sexual interest and arousal disorder is personally distressing for women. To better understand the mechanism of the candidate therapeutic, flibanserin, we determined its effects on an index of brain glucose metabolism.
We hypothesized that chronic treatment with flibanserin would alter metabolism in brain regions associated with serotonergic function and female sexual behavior.
In a crossover design, eight adult female common marmosets (Calithrix jacchus) received daily flibanserin or vehicle. After 7-12 weeks of treatment, the glucose metabolism radiotracer [(18) F]fluorodeoxyglucose (FDG) was administered to each female immediately prior to 30 minutes of interaction with her male pairmate, after which females were anesthetized and imaged by positron emission tomography. Whole-brain normalized images were analyzed with anatomically defined regions of interest. Whole-brain voxelwise mapping was used to explore treatment effects. Correlations were examined between alterations in metabolism and pairmate social grooming.
Changes in metabolism associated with flibanserin were determined for dorsal raphe, medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus, and field cornu ammonis 1 (CA1) of the hippocampus.
In response to chronic flibanserin, metabolism in mPOA declined, and this reduction correlated with increases in pairmate grooming. A cluster of voxels in frontal cortico-limbic regions exhibited reduced metabolism in response to flibanserin and overlapped with a voxel cluster in which reductions in metabolism correlated with increases in pairmate grooming. Finally, reductions in mPOA metabolism correlated with increases in metabolism in a cluster of voxels in somatosensory cortex.
Taken together, these results suggest that flibanserin-induced reductions in female mPOA neural activity increase intimate affiliative behavior with male pairmates.
女性性兴趣和唤起障碍令女性个人痛苦不堪。为了更好地理解候选治疗药物氟班色林的作用机制，我们确定了其对脑葡萄糖代谢指标的影响。
我们假设，长期使用氟班色林会改变与血清素功能及女性性行为相关脑区的代谢。
采用交叉设计，八只成年雌性普通狨猴（Callithrix jacchus）每日接受氟班色林或赋形剂治疗。治疗7至12周后，在每只雌性与雄性配对伙伴互动30分钟之前，立即给其注射葡萄糖代谢放射性示踪剂[（18）F]氟脱氧葡萄糖（FDG），之后对雌性进行麻醉并通过正电子发射断层扫描成像。使用解剖学定义的感兴趣区域分析全脑标准化图像。采用全脑体素映射来探究治疗效果。检查代谢变化与配对伙伴社交梳理之间的相关性。
确定氟班色林相关的背缝核、内侧前额叶皮质（mPFC）、下丘脑内侧视前区（mPOA）、下丘脑腹内侧核以及海马体角回1区（CA1）的代谢变化。
长期使用氟班色林后，mPOA的代谢下降，这种下降与配对伙伴梳理行为的增加相关。额叶皮质-边缘区域的一组体素对氟班色林反应显示代谢降低，且与一组代谢降低与配对伙伴梳理行为增加相关的体素簇重叠。最后，mPOA代谢的降低与体感皮质中一组体素的代谢增加相关。
综上所述，这些结果表明，氟班色林诱导的雌性mPOA神经活动减少会增加与雄性配对伙伴的亲密依恋行为。
