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

Sara de la Salle; Justin Piche; Brittany Duncan; Joëlle Choueiry; Molly Hyde; Robert Aidelbaum; Ashley Baddeley; Danielle Impey; Noreen Rahmani; Vadim Ilivitsky; Verner Knott

doi:10.1177/02698811241246854

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

J Psychopharmacol. 2024 Apr 22:2698811241246854. doi: 10.1177/02698811241246854. Online ahead of print.

Authors

Sara de la Salle^{1

2}, Justin Piche³, Brittany Duncan⁴, Joëlle Choueiry^{1

3}, Molly Hyde⁵, Robert Aidelbaum⁶, Ashley Baddeley¹, Danielle Impey², Noreen Rahmani², Vadim Ilivitsky⁷, Verner Knott^{1

3}

Affiliations

¹ The Royal's Institute of Mental Health Research at The Royal, Ottawa, ON, Canada.
² School of Psychology, University of Ottawa, Ottawa, ON, Canada.
³ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
⁴ Department of Psychology, Carleton University, Ottawa, ON, Canada.
⁵ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁶ School of Psychology, University of Toronto, Toronto, ON, Canada.
⁷ The Royal Ottawa Mental Health Centre, Ottawa, ON, Canada.

PMID: 38647196
DOI: 10.1177/02698811241246854

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 GABA_A (lorazepam: 1 mg) and GABA_B 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 GABA_B receptor signaling in anxiety-associated gating dysregulation.

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