RESUMO
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.
Assuntos
Metanfetamina , Ratos , Feminino , Animais , Metanfetamina/farmacologia , Óxido Nítrico , Peptídeo Intestinal Vasoativo , Progesterona/farmacologia , Lubrificação , AutoadministraçãoRESUMO
INTRODUCTION: Recreational psychostimulants have been associated with increased sexual activity or changes in sexual function in women, but every drug in this class has not shown consistent sexual effects in scientific studies. Further, some studies in female animal models may recapitulate the effects observed in humans, while others produce conflicting results. Overall, though, published studies on the sexual effects of recreational stimulants in women are lacking. OBJECTIVES: The objective of this manuscript was to review the published sexual effects of prominent recreational psychostimulants in women and in the female rat model. METHODS: Literature searches for "any years" were performed through PubMed and Google Scholar. Keywords for the searches included "amphetamine," "methamphetamine," "MDMA," "ecstasy," "3,4-methylenedioxymethamphetamine," "cocaine," "caffeine," "sex," "sexual," "female," and "women." Studies in humans and using animal models were included. RESULTS: Older studies have shown that amphetamine produces a positive sexual effect in women, but often the sample size was too small to draw generalizable conclusions. Methamphetamine also has a positive effect on several sexual domains in women, as well as on vaginal lubrication. 3,4-Methylenedioxymethamphetamine may have a negative or positive effect on sexual activity, but often enhances the sensual aspects of sex. Though low doses of cocaine may heighten the sexual experience, most women who use cocaine experience negative sexual effects. Caffeine has been shown to enhance a physiological measure of arousal, vaginal blood flow, but based on our searches, no studies have investigated the subjective sexual effects of the drug. CONCLUSION: Different recreational psychostimulants produce varying effects on sexual behavior and responses in women and female animal models, but more research is needed to understand these effects better.