Methamphetamine-induced vaginal lubrication in rats

Abstract

Abstract Background Based on previous studies of vaginal lubrication as well as our own previously reported interview study of women who self-reported methamphetamine (meth)–induced vaginal lubrication, in the current study we sought to determine the potential dose-response relationship leading to meth-induced vaginal lubrication. We also developed an animal model to study the reported effects and examine potential mechanisms mediating this phenomenon. Aim We sought to characterize the effects of meth on vaginal lubrication in an animal model with the aim of providing a potential framework for new mechanisms that incorporate novel therapeutic agents for the treatment of vaginal dryness. Methods Vaginal lubrication was measured via insertion of a preweighed, cotton-tipped swab into the vaginal canal of anesthetized rats following treatment with various doses of intravenous (IV) meth, up to 0.96 mg/kg, and after additional pharmacological manipulations, including administration of a nitric oxide synthase inhibitor and an estrogen receptor antagonist. Plasma signaling molecules, including estradiol, progesterone, testosterone, nitric oxide, and vasoactive intestinal polypeptide, were measured immediately before and at 9 time points after IV meth administration. Blood was collected via a previously implanted chronic indwelling jugular catheter and analyzed by use of commercially available kits per the manufacturer’s instructions. Outcomes Outcomes for this study include the measurement of vaginal lubrication in anesthetized rats following various pharmacological manipulations and plasma levels of various signaling molecules. Results Meth dose-dependently increased vaginal lubrication in anesthetized female rats. Meth significantly increased plasma levels compared to baseline of estradiol (2 and 15 minutes after meth infusion) as well as progesterone, testosterone, and nitric oxide (10 minutes after meth infusion). Also, vasoactive intestinal polypeptide decreased significantly compared to baseline for 45 minutes following meth infusion. Our data further suggest that nitric oxide, but not estradiol, is critical in the production of vaginal secretions in response to meth. Clinical Implications This study has far-reaching implications for women who are suffering from vaginal dryness and for whom estrogen therapy is unsuccessful, as the investigation has demonstrated that meth presents a novel mechanism for producing vaginal lubrication that can be targeted pharmacologically. Strengths and Limitations This study is, to our knowledge, the first performed to measure the physiological sexual effects of meth in an animal model. Animals were anesthetized when they were administered meth. In an ideal situation, animals would be self-administering the drug to recapitulate better the contingent nature of drug taking; however, this method was not feasible for the study reported here. Conclusion Methamphetamine increases vaginal lubrication in female rats through a nitric oxide–dependent mechanism.