Differences in sympathetic nervous system activity and NMDA receptor levels within the hypothalamic paraventricular nucleus in rats with differential ejaculatory behavior

Jia-Dong Xia, Jie Chen, Bai-Bing Yang, Hai-Jian Sun, Guo-Qing Zhu, Yu-Tian Dai, Jie Yang, Zeng-Jun Wang, Jia-Dong Xia, Jie Chen, Bai-Bing Yang, Hai-Jian Sun, Guo-Qing Zhu, Yu-Tian Dai, Jie Yang, Zeng-Jun Wang

Abstract

Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system (SNS) activity and expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus of the hypothalamus (PVN). Male rats were classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460 ± 480 mV, 1660 ± 600 mV, and 1680 ± 490 mV, respectively (P = 0.71). However, SNS sensitivity was remarkably different between the groups (P < 0.01), being 28.9% ± 8.1% in "sluggish," 48.4% ± 7.5% in "normal," and 88.7% ± 7.4% in "rapid" groups. Compared with "normal" ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of "rapid" ejaculators was significantly higher, whereas it was significantly lower in "sluggish" ejaculators (P = 0.01). In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity (r = 0.876, P = 0.02). This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN.

Keywords: N-methyl-D-aspartic acid receptor; ejaculation; paraventricular nucleus; sympathetic nervous system.

Conflict of interest statement

All authors declared no competing interests

Figures

Figure 1
Figure 1
Mean ejaculation frequency (the total number of ejaculations during the 30 min test) (n = 33).
Figure 2
Figure 2
(a) Representative recordings showing LSNA changes from baseline after HEX treatment (30 mg kg−1 injected into the carotid vein). (b) LSNA sensitivity of “sluggish,” “normal,” and “rapid” ejaculating rats. *P < 0.01, “normal” rats compared with “sluggish” rats; #P < 0.01, “normal” rats compared with “rapid” rats. HEX: hexamethonium hydrochloride; LSNA: lumbar sympathetic nerve activity; R-LSNA: raw LSNA; I-LSNA: integrated LSNA.
Figure 3
Figure 3
(a) Immunohistochemical analysis of NMDANR1 distribution (brown color) in the PVN in “rapid,” “normal,” and “sluggish” rats. (b) Bar graph showing the number of NMDANR1-positive cells in the PVN. Values are presented as mean ± s.e. *P < 0.01, “normal” group compared with the “rapid” group; #P < 0.01, “normal” group compared with the “sluggish” group. 3V: third ventricle; NMDANR1: N-methyl-D-aspartic acid-NR1; PVN: paraventricular nucleus of the hypothalamus; s.e.: standard error.
Figure 4
Figure 4
Western blot analysis of NMDANR1 normalized against GAPDH in the punched PVN samples of “sluggish,” “normal,” and “rapid” rats. *P < 0.01, “normal” group compared with the “sluggish” group; #P < 0.01, “normal” group compared with the “rapid” group. NMDANR1: N-methyl-D-aspartic acid-NR1; GAPHD: glyceraldehyde-3-phosphate dehydrogenase; PVN: paraventricular nucleus of the hypothalamus.
Figure 5
Figure 5
Positive correlation between the expression of NMDANR1 in the paraventricular nucleus of the hypothalamus and sympathetic nervous system sensitivity (r = 0.876, P = 0.02). NMDANR1: N-methyl-D-aspartic acid-NR1.

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