Methamphetamine-Induced Vaginal Lubrication & Associated Hormonal Changes

Abstract

ABSTRACT Introduction Vaginal dryness is an issue that affects millions of women, creating a situation that often leads to painful sexual experiences and diminished pleasure and self-esteem. Though the physiology of vaginal lubrication in response to sexually arousing stimuli is established, no treatment, other than topical lubricants, is available for women suffering from vaginal dryness. Previous research from our lab reported that female methamphetamine (meth) users experience immediate and noticeable vaginal lubrication when they inject the drug intravenously (IV). A warming or flushing sensation spreading from the chest area down into the pelvic region accompanied this lubrication. Understanding the mechanisms mediating this previously undescribed phenomenon may reveal a potential target for future pharmaceutical development to enhance a woman's natural levels of vaginal lubrication. We have reported that injections of meth also increase vaginal lubrication in rats in a dose-dependent manner. Plasma levels of several signaling molecules known to influence vaginal lubrication, including the steroid hormones estradiol, progesterone, and testosterone, as well as the gaseous vasodilator nitric oxide, increase at specific time points following IV meth in female rats. Accordingly, we were able to decrease the amount of vaginal fluid produced by pre-treating the animals with the nitric oxide synthase inhibitor, L-NAME, prior to meth. Objective The present work expands the aforementioned findings by measuring plasma levels of vasoactive intestinal polypeptide (VIP), an established mediator of female sexual arousal, and corticosterone, a steroid hormone implicated in drug addiction, after IV injections of meth. We also determined the involvement of estradiol in meth-induced vaginal lubrication using an estrogen receptor antagonist. Methods We implanted adult female Wistar rats with chronic indwelling jugular catheters and allowed them at least one week to recover from surgery. We pre-treated the rats with fulvestrant, an estrogen receptor antagonist, and then anesthetized them with isoflurane gas before injecting them intravenously with meth via the implanted catheter. A pre-weighed cotton-tipped swab, inserted into the vaginal canal, collected fluid secreted following the administration of meth. The change in the weight of the swab before and after meth indicated the amount of fluid produced. In a separate group of rats, we used the jugular catheter to remove blood at various time points (1-60 min) following the meth injections to measure plasma levels of VIP and corticosterone. Results Although we have not yet completed these experiments, we hypothesize that the inhibition of estrogen receptors will reduce meth-induced vaginal lubrication similar to the reduction produced by L-NAME. Further, we predict that both VIP and corticosterone levels will increase between 5 and 20 min after the injections of meth, similarly to the other signaling molecules we measured previously. Conclusions These findings have far-reaching and potentially life-changing implications, as the majority of women will experience vaginal dryness a least once in their lifetimes, if not chronically. The underlying mechanisms of meth-induced vaginal lubrication may provide the necessary pharmacological target to treat vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Goeders is on the Scientific Advisory Boards for Embera NeuroTherapeutics and JanOne; however, the work of these companies is unrelated to the submitted abstract.