Are Women Sensitive to the Acute Anxiolytic Effect of Diazepam?

Camila Danielle,Aragao Almeida

doi:10.4172/2167-1044.1000235

Abstract

Objective: Several studies have shown the influence of ovarian hormones on the GABAergic system. As women are naturally exposed to monthly fluctuation of these hormones, it is possible that their response to benzodiazepines also change over the ovarian cycle. Bearing this in mind, this study aimed to evaluate the possible influence of the ovarian cycle of healthy women on the acute effect of diazepam. Methods: Forty subjectively healthy women were selected and randomly allocated to two different groups, according to their ovarian cycle phase, follicular (6 to 10 days from the first day of the cycle) or luteal (5 to 10 days after detection of urinary LH peak). Both groups completed the Video-Monitored Stroop Color-Word Test (VMSCWT), an experimental model of anxiety, under the influence of diazepam (10 mg) or placebo. Psychological parameters (State-Trait Anxiety Inventory, Self-evaluation of Tension Level, Visual Analogue Mood Scale) and physiological parameters (heart rate and gastrocnemius electromyogram activity) were evaluated throughout the test. All the data obtained were analyzed using analysis of variance (ANOVA) followed by Tukey’s test for post hoc comparisons, both at the 5% significance level. Results: The results showed that, in the follicular phase, women did not respond to the anxiolytic action of diazepam, although a sedative effect was observed; while in the luteal phase, there was no response to either sedative or anxiolytic actions. As a control for the experimental conditions, a group of 18 men was also administered to the VMSCWT. The results confirmed that both the anxiogenic test and the administered drug were working as expected, since diazepam managed to prevent the anxiety induced by the test. Conclusion: Therefore, the present findings indicate that the ovarian cycle can alter the effects of the acute administration of diazepam, which can vary from no effect to sedation, without going through anxiolysis.

Highlights

The ovarian hormones as all steroid hormones are synthesized from cholesterol, and due to its lipophilicity, have easy access to all cells and organs, including the central nervous system (CNS) [1]
It has been demonstrated that the 3α-hydroxysteroid is a potent anxiolytic, anticonvulsant, sedative/hypnotic and anesthetic, which exerts its effects through allosteric modulation of the gamma-aminobutyric acid (GABA) receptor complex
The results of Experiment I showed that women in the follicular ovarian phase presented no response to the anxiolytic action of diazepam, since the increase in anxiety promoted by the anxiogenic Video-Monitored Stroop Color-Word Test (VMSCWT) was neither prevented nor reduced by the drug, as demonstrated by the State-Trait Anxiety Inventory (STAI)-state scores, the self-evaluated tension levels and the values of the tranquilization factor of the Visual Analogue Mood Scale (VAMS)

Summary

Introduction

The ovarian hormones as all steroid hormones are synthesized from cholesterol, and due to its lipophilicity, have easy access to all cells and organs, including the central nervous system (CNS) [1]. These hormones influence the function of many nervous cells, playing an important role in coordinating a number of physical and behavioral changes related to reproductive cycle [2]. Studies are highlighting the critical role that ovarian hormones may have on the organization of non-reproductive behavior, especially in response to stress and anxiety [3,4,5,6]. It has been suggested that alloP enhances GABA-mediated inhibition during states of hyperexcitability of the CNS, such as stress or anxiety [9,10,11,12,13]

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Results

Discussion

Conclusion