Department of Urology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.
Andrology. 2022 May;10(4):808-817. doi: 10.1111/andr.13171. Epub 2022 Mar 15.
The central molecular mechanisms of nonorganic erectile dysfunction remains unknown.
This study aimed to investigate the association of dopaminergic neurons projecting to the nucleus accumbens of male rats with nonorganic erectile dysfunction.
MATERIALS/METHODS: Nonorganic erectile dysfunction was induced by chronic mild stress. The sucrose consumption test, sexual behavior test, and apomorphine test were carried out to select depression-like rats with erectile dysfunction. These rats were considered as nonorganic erectile dysfunction model rats. Dopamine D1/D2 receptor agonist/antagonist was infused into the nucleus accumbens to observe the effect on sexual behavior. Dopaminergic projections to the nucleus accumbens were labeled with both the retrograde tracer FluoroGold injected into the nucleus accumbens and tyrosine hydroxylase. The expression level of tyrosine hydroxylase in dopaminergic neurons projecting to the nucleus accumbens in the ventral tegmental area was measured. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the nucleus accumbens were also measured.
Nonorganic erectile dysfunction was proved by the sucrose consumption test, sexual behavior test, and apomorphine test in model rats. After central infusion of the dopamine D2 receptor agonist into the nucleus accumbens, the recovery of erectile function, sexual arousal, and motivation were indicated by increased intromission ratio and decreased mount latency. Decreased expression levels of dopamine D2 receptors and tyrosine hydroxylase in the nucleus accumbens and decreased expression level of tyrosine hydroxylase in the dopaminergic neurons projecting to the nucleus accumbens were observed in model rats.
These results suggest the impairment of dopaminergic neurons projecting to the nucleus accumbens and dopamine D2 signaling in the nucleus accumbens, causing the suppression of erectile function, sexual arousal, and motivation.
These results suggest that the impaired dopamine D2 receptor pathway in the nucleus accumbens may be one of the main pathway involved in the development of nonorganic erectile dysfunction in the present model.
非器质性勃起功能障碍的中心分子机制尚不清楚。
本研究旨在探讨投射到雄性大鼠伏隔核的多巴胺能神经元与非器质性勃起功能障碍的关系。
材料/方法:采用慢性轻度应激诱导非器质性勃起功能障碍。通过蔗糖消耗试验、性行为试验和阿扑吗啡试验选择勃起功能障碍伴抑郁的大鼠作为非器质性勃起功能障碍模型大鼠。将多巴胺 D1/D2 受体激动剂/拮抗剂注入伏隔核,观察对性行为的影响。用逆行示踪剂 FluoroGold 注射到伏隔核和酪氨酸羟化酶标记投射到伏隔核的多巴胺能神经元。测量腹侧被盖区投射到伏隔核的多巴胺能神经元中酪氨酸羟化酶的表达水平。还测量了伏隔核中多巴胺 D1/D2 受体和酪氨酸羟化酶的表达水平。
模型大鼠通过蔗糖消耗试验、性行为试验和阿扑吗啡试验证实存在非器质性勃起功能障碍。中央注入多巴胺 D2 受体激动剂后,插入率增加,潜伏期缩短,表明勃起功能、性唤起和动机恢复。模型大鼠的伏隔核中多巴胺 D2 受体和酪氨酸羟化酶表达水平降低,投射到伏隔核的多巴胺能神经元中酪氨酸羟化酶表达水平降低。
这些结果表明,投射到伏隔核的多巴胺能神经元和伏隔核中的多巴胺 D2 信号受损,导致勃起功能、性唤起和动机受到抑制。
这些结果提示,伏隔核中受损的多巴胺 D2 受体通路可能是本模型中非器质性勃起功能障碍发展的主要通路之一。