Influence of GABAA and GABAB receptor activation on auditory sensory gating and its association with anxiety in healthy volunteers

J Psychopharmacol. 2024 Jun;38(6):532-540. doi: 10.1177/02698811241246854. Epub 2024 Apr 22.

Abstract

Background: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA).

Aims/methods: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety.

Results: Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety.

Conclusions: These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABAB receptor signaling in anxiety-associated gating dysregulation.

Keywords: P50 event-related potential; anxiety; auditory sensory gating; baclofen; lorazepam; γ-aminobutyric acid.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anxiety* / metabolism
  • Baclofen* / pharmacology
  • Double-Blind Method
  • Evoked Potentials, Auditory / drug effects
  • Evoked Potentials, Auditory / physiology
  • Female
  • GABA-A Receptor Agonists / pharmacology
  • GABA-B Receptor Agonists* / pharmacology
  • Healthy Volunteers
  • Humans
  • Lorazepam* / pharmacology
  • Male
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Receptors, GABA-B* / drug effects
  • Receptors, GABA-B* / metabolism
  • Sensory Gating* / drug effects
  • Young Adult

Substances

  • Baclofen
  • Lorazepam
  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • GABA-A Receptor Agonists
  • Receptors, GABA-A