GABAB Receptors and Cognitive Processing in Health and Disease

Curr Top Behav Neurosci. 2022:52:291-329. doi: 10.1007/7854_2021_231.

Abstract

GABAB receptors are implicated in numerous central nervous system-based behaviours and mechanisms, including cognitive processing in preclinical animal models. Homeostatic changes in the expression and function of these receptors across brain structures have been found to affect cognitive processing. Numerous preclinical studies have focused on the role of GABAB receptors in learning, memory and cognition per se with some interesting, although sometimes contradictory, findings. The majority of the existing clinical literature focuses on alterations in GABAB receptor function in conditions and disorders whose main symptomatology includes deficits in cognitive processing. The aim of this chapter is to delineate the role of GABAB receptors in cognitive processes in health and disease of animal models and human clinical populations. More specifically, this review aims to present literature on the role of GABAB receptors in animal models with cognitive deficits, especially those of learning and memory. Further, it aims to capture the progress and advances of research studies on the effects of GABAB receptor compounds in neurodevelopmental and neurodegenerative conditions with cognitive dysfunctions. The neurodevelopmental conditions covered include autism spectrum disorders, fragile X syndrome and Down's syndrome and the neurodegenerative conditions discussed are Alzheimer's disease, epilepsy and autoimmune anti-GABAB encephalitis. Although some findings are contradictory, results indicate a possible therapeutic role of GABAB receptor compounds for the treatment of cognitive dysfunction and learning/memory impairments for some of these conditions, especially in neurodegeneration. Moreover, future research efforts should aim to develop selective GABAB receptor compounds with minimal, if any, side effects.

Keywords: Animal models; Cognition; GABAB receptors; Humans; Learning; Memory; Neurodegeneration; Neurodevelopmental disorders; Pharmacotherapy; Treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Cognition
  • Cognition Disorders*
  • Disease Models, Animal
  • Humans
  • Receptors, GABA-B* / metabolism
  • gamma-Aminobutyric Acid

Substances

  • Receptors, GABA-B
  • gamma-Aminobutyric Acid