Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: A randomized, double-blind study
Pflanz CP., Pringle A., Filippini N., Warren M., Gottwald J., Cowen PJ., Harmer CJ.
© 2014 Springer-Verlag Berlin Heidelberg. Abstract Rationale: Benzodiazepines, such as diazepam, are anxiolytic-sedative drugs, used for the treatment of several different disorders. The pharmacological mechanism of action of benzodiazepines is well understood; however, it remains unclear which neural networks and systems are involved in translating these neurochemical actions into their therapeutic effects. Objectives: The objective of this study was to investigate the effects of 7-day diazepam administration compared to placebo on resting-state functional connectivity in healthy adults independent of any task. Methods: Thirty-four healthy participants were randomly assigned to receive either diazepam (N=17) or placebo (15 mg daily for 7 days) and underwent resting-state functional magnetic resonance acquisition. Model-free data analysis was performed using independent component analysis and dual regression. Results: Consistent with previous research, 11 resting-state networks were identified. Increased connectivity in response to diazepam administration was found in the medial visual network and middle/inferior temporal network. Diazepam did not cause any decreases in functional connectivity. Conclusions: Diazepam administration increases functional connectivity in areas of emotional processing independent of any task. Diazepam also enhanced functional connectivity in the medial visual system, which is a brain region rich in GABAA receptors, and shows high binding of GABAergic drugs. These increases in functional connectivity are characteristic of CNS depressants.