The role of tyrosine hydroxylase within dapoxetine-assisted therapy against premature ejaculation

Mol Biol Rep. 2023 Apr;50(4):3515-3523. doi: 10.1007/s11033-022-08140-3. Epub 2023 Feb 14.

Abstract

Background: There are several investigations that have revealed that cerebral dopamine (DA) plays a pivotal role in the occurrence of premature ejaculation (PE). Although tyrosine hydroxylase (TH) is an essential enzyme for the synthesis of DA, only few investigations have described the role of TH in regulation mechanisms for ejaculation till now. To investigate whether there is a correlation between TH expression level in the brain and different ejaculation behavior in rats. Then explore whether the TH expression in the brain will change after acute dapoxetine treatment in rats with Rapid ejaculation.

Methods and results: Rats (male, S-D rats, 6-8 weeks) were separated into three groups based on their ejaculation frequency: Rapid, Normal, and Sluggish. Expression level of DA in the brain was determined by enzyme-linked immune sorbent assay (ELISA) kit, TH expression level in the brain was determined by immunohistochemistry and Western Blot (WB) techniques. Among the three groups, DA and TH expression level were the highest in the Rapid ejaculation group, while the lowest was the Sluggish ejaculation group. The results also showed that TH level was positively associated with ejaculation frequency (r = 0.8038, P < 0.001) and negatively associated with ejaculation latency (r=-0.6199, P = 0.018). Furthermore, acute dapoxetine therapy in rats with Rapid ejaculation downregulated TH level in the brain.

Conclusion: Changes in ejaculation behavior were significantly linked with TH level. Upregulated TH in selected brain regions related with ejaculation could cause rapid ejaculation. The effect of dapoxetine in prolonging ejaculation could be related to TH downregulation within the brain.

Keywords: Animal model; Premature ejaculation; Sexual behavior; Tyrosine hydroxylase.

MeSH terms

  • Animals
  • Humans
  • Male
  • Premature Ejaculation* / drug therapy
  • Rats
  • Selective Serotonin Reuptake Inhibitors
  • Treatment Outcome
  • Tyrosine 3-Monooxygenase

Substances

  • dapoxetine
  • Tyrosine 3-Monooxygenase
  • Selective Serotonin Reuptake Inhibitors