Abstract
The GABAB receptor is activated by the main inhibitory neurotransmitter of the central nervous system, the γ-aminobutyric acid (GABA). The receptor is expressed in almost all neuronal and glial cells and plays a central role in the modulation of many physiological and pathological processes. The GABAB receptor has been considered for years as an interesting target for the treatment of spasticity, pain, addiction, anxiety or depression. This has prompted many studies aiming at understanding the activation of the receptor and its modulation. While it belongs to the super-family of G protein-coupled receptors (GPCRs), it was rapidly evident that the GABAB receptor is peculiar in the variety of allosteric modulations governing its activation. Here, I wish to gather the different aspects of the GABAB receptor allosteric modulation. After presenting the main small molecule allosteric modulators known to date, the intramolecular transitions controlling the receptor activation will be summarized. In addition, recent findings obtained in the last decade on the existence of GABAB receptor complexes and their influence on the receptor function will be introduced, including the GABAB receptor oligomers and the auxiliary proteins associated with the receptor. These new concepts will certainly be of major interest in the future analysis of GABAB receptor allosteric modulation.