In the US
methamphetamine is considered a first-line treatment for
attention-deficit hyperactivity disorder. It is also a common
drug of abuse. Reports in patients and abusers suggest its use results in
impotence. The efficacy of
phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies, we determined if the rat is a suitable animal model for the physiological effects of
methamphetamine on erectile function, and if a PDE5i (
tadalafil) has an effect on erectile function following
methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg
methamphetamine i.p. Chronically treated animals received escalating doses of
methamphetamine [2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)] i.p. daily for 3 weeks and erectile function compared with untreated controls. The effect of co-administration of
tadalafil was also investigated in rats acutely and chronically treated with
methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies, we observed a significant increase in the rates of spontaneous erections after
methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6 mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function.
Tadalafil treatment reversed this effect. In chronically treated animals, the ICP/BP ratio following 4 and 6 mA stimulation decreased by approximately 50% compared with untreated animals and
erectile dysfunction (ED) was also reversed by
tadalafil. Overall, our data suggest that the rat is a suitable animal model to study the physiological effect of
methamphetamine on erectile function. Our work also provides a rationale for treating patients that report ED associated with
therapeutics-containing
methamphetamine or
amphetamine with PDE5i.