Effect of Hyperforin-Enriched Extract on Pro-Ejaculatory Effect of 8-Hydroxy-2-(Di-N-Propylamino)Tetralin in Anesthetized Rats

Abstract

Premature ejaculation is the most common male sexual dysfunction and, yet, no approved effective therapies are currently available. We studied the in vivo effectiveness of hyperforin (HF), a concentrated extract of Hypericum perforatum in an experimental model for the expulsion phase of ejaculation in anesthetized rats. The ejaculation model involved inducing rhythmic bulbospongiosus (BS) muscle contractions in male rats under urethane anesthesia (1.2 g/kg subcutaneously) by transiently raising the internal urethral pressure with saline infusion for 2 seconds at a rate of 116 microL/s. Electrodes in the BS muscles recorded the electrical activity during the contractions as a cluster of bursts on the electromyogram. Injection of the 5-hydroxytryptamine type 1A agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (0.4 mg/kg subcutaneously) intensified the BS muscle contractions induced by increases in urethral pressure. Administration of 8-OH-DPAT strongly accelerated the ejaculation in the vehicle-treated rats and the amplitude of electrical discharges and the duration of electrical bursts accompanying the increases in urethral pressure were increased from baseline by 203.2% +/- 32.9% and 178.1% +/- 22.9%, respectively. The HF extract reduced the effects of 8-OH-DPAT on ejaculation at lower doses when tested in the dose range of 5 to 80 mg/kg. The reduction in the amplitude of bursts with HF extract remained unchanged after a midthoracic spinal transection, suggesting that the action of HF is either at the spinal ejaculation generator or directly on the neurons innervating the BS muscles. This is the first report of the effect of HF in a rat model of ejaculation. HF can be considered a novel new treatment of premature ejaculation.