Introduction: The purpose of this study was to induce hyperprolactinemia in adult male rats and determine its effect on the central and peripheral mediated neurogenic as well as myogenic mechanisms of erectile functionadysfunction in a rat model. The use of penile re¯exes in awake animals was used to test the effect of both central and peripheral mechanisms. Electrical stimulation of the cavernous nervous was used to test peripheral neural function and intracorporal injection of papaverine was used to test the intactness of the corporal smooth muscles. These mechanisms were further explored by administration of testosterone. Methods: Eighteen Fisher-344 200 ± 250 g rats aged 10 weeks were used in this study. Group 1 (n 6) hyperprolactinemia was induced with subcutaneous (SQ) injection of 5 mg rat prolactin (NIDDK-r-PRL-B-7, biopotency 25 IUamg) in two divided doses daily for 1 week. Testosterone propionate 100 mgakg dissolved in sesame oil was given intramuscularly on day 1 (weekly dose). Group 2 (n 6) control animals received SQ injection of vehicle twice daily and sesame oil IaM on day 1. Group 3 (n 6) received testosterone propionate. Penile re¯exes (erections, cups,¯ips and clusters) were assessed prior to induction (63) of and following one-week state of hyperprolactinemia (day 5, 6 and 7). All animals were trained three times before recording the penile re¯exes. The penile re¯exes being averaged to give a single composite score for each animal. All animals underwent dissections that isolated the cavernosal bodies and cavernosal nerves. Cavernous nerves were activated and intracorporal pressures were recorded at increasing current magnitude (range 0.5 ± 10 mA). Following that corporal smooth muscle reactivity was determined by increasing injection of papaverine (100 ± 3000 mg). Concentration response curves (CRCs) were then generated by plotting percent change (fractional change to make standardized comparison) to increasing neurostimulation or papaverine concentrations at half-log increments. Serum prolactin was determined by rPRL radioimmunoassay Kit-Amersham while serum testosterone was determined Testosterone ELISA Kit-Neogen. Results: Penile re¯exes were normal in all groups at the start of experiment but after 1 week of hyperprolactinemia, re¯exes were totally abolished in hyperprolactinemia rats (Group 1) and unchanged in Groups 2 and 3. Response to cavernous nerve activation and resulting rise in intracorporal pressure to increasing current (range 0.5 ± 10 mA) were statistically non-signi®cant in any groups. Similarly the intracorporal pressure response to pharmacologic erection induced by papaverine (100 ± 3000 mg) were also non-statistically signi®cant in any groups. Serum prolactin level in all rats receiving prolactin were b 500 ngaml and the rat group receiving testosterone, serum level were b 206higher than the control rat. Conclusions: This approach allowed more clear separation of central and peripheral mechanism of erection. This study shows a central neurological effect of hyperprolactinem...