The effect of methamphetamine on an animal model of erectile function.
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.
Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA.
M T
MT
Tar
L R
LR
Martinez
J D
JD
Nosanchuk
K P
KP
Davies
D000818:Animals; D002243:Carbolines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000188:drug therapy*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D000068581:Tadalafil
D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D008694:Methamphetamine; D000068581:Tadalafil
erectile dysfunction; methamphetamine; rat model; tadalalfil