Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: a randomized, double-blind study

Psychopharmacology (Berl). 2015 Jun;232(12):2139-47. doi: 10.1007/s00213-014-3844-3. Epub 2014 Dec 25.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Anxiety Agents / pharmacology*
  • Brain / drug effects
  • Diazepam / pharmacology*
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / drug effects*
  • Receptors, GABA-A / drug effects
  • Rest
  • Visual Pathways / drug effects
  • Young Adult

Substances

  • Anti-Anxiety Agents
  • Receptors, GABA-A
  • Diazepam