The effect of methamphetamine on an animal model of erectile function.

Abstract

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.

• Authors: M T Tar, L R Martinez, J D Nosanchuk, K P Davies
• Journal: Andrology (Andrology) Vol. 2 Issue 4 Pg. 531-6 (Jul 2014) ISSN: 2047-2927 [Electronic] England
• PMID: 24706617 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2014 American Society of Andrology and European Academy of Andrology.

Chemical References

• Carbolines
• Phosphodiesterase 5 Inhibitors
• Methamphetamine
• Tadalafil

Topics

• Animals
• Carbolines (therapeutic use)
• Disease Models, Animal
• Erectile Dysfunction (drug therapy)
• Male
• Methamphetamine (pharmacology)
• Penile Erection (drug effects)
• Phosphodiesterase 5 Inhibitors (therapeutic use)
• Rats, Sprague-Dawley
• Tadalafil