Abstract

In this study, a simple duel-optical spectroscopic imaging apparatus capable of simultaneously determining relative changes in brain oxy-and deoxy-hemoglobin concentrations was used following administration of the anxiolytic compound diazepam in mice with strong dominant (Dom) and submissive (Sub) behavioral traits. Three month old mice (n = 30) were anesthetized and after 10 min of baseline imaging, diazepam (1.5 mg/kg) was administered and measurements were taken for 80 min. The mouse head was illuminated by white light based LED's and diffused reflected light passing through different channels, consisting of a bandpass filter and a CCD camera, respectively, was collected and analyzed to measure the hemodynamic response. This work's major findings are threefold: first, Dom and Sub animals showed statistically significant differences in hemodynamic response to diazepam administration. Secondly, diazepam was found to more strongly affect the Sub group. Thirdly, different time-series profiles were observed post-injection, which can serve as a possible marker for the groups' differentiation. To the best of our knowledge, this is the first report on the effects of an anxiolytic drug on brain hemodynamic responses in mice using diffused light optical imaging.

Highlights

  • Depressive and anxiety disorders are clinically problematic with a majority of cases showing multiple recurrences and frequent progression to the chronic stage [1, 2]

  • The strong changes in ΔHbr seen among Sub mice in comparison to other groups may be supported by our recent study showing differential effects of diazepam on these mice [30]

  • We have showed the effects of the anxiolytic compound diazepam on mouse brain hemodynamic parameters through intact scalp using a relatively simple and inexpensive diffuse-reflectance optical imaging

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Summary

Introduction

Depressive and anxiety disorders are clinically problematic with a majority of cases showing multiple recurrences and frequent progression to the chronic stage [1, 2]. Therapeutic compounds’ efficacy is assessed mainly based on behavioral changes in both preclinical and clinical studies, while objective physiological parameters of treatment’s success have yet to be developed. A member of the benzodiazepine family, acts through modulation of GABAergic neurotransmission by producing anxiolytic, sedative or/and anticonvulsive effects [9]. It is used in treatment of disorders characterized by anxiety, agitation, tremors, delirium, seizures, as well as hallucinations resulting from alcohol withdrawal [10, 11]. The influence of the psychotropic drugs on brain hemodynamics needs to be more clearly understood

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