GABA(B) receptor alterations as indicators of physiological and pharmacological function

Abstract

Given the widespread distribution of GABA(B) receptors throughout the central nervous system, and within certain peripheral organs, it is likely their selective pharmacological manipulation could be of benefit in the treatment of a variety of disorders. Studies aimed at defining the clinical potential of GABA(B) receptor agonists and antagonists have included gene deletion experiments, examination of changes in receptor binding, subunit expression and function in diseased tissue, as well as after the chronic administration of drugs. The results indicate that a functional GABA(B) receptor requires the combination of GABA(B(1)) and GABA(B(2)) subunits, that receptor function does not always correlate with subunit expression and receptor binding, and that GABA(B) receptor modifications may be associated with the clinical response to antidepressants, mood stabilizers, and GABA(B) receptor agonists and antagonists. Moreover, changes in GABA(B) binding or expression suggest this receptor may be involved in mediating symptoms associated with chronic pain, epilepsy and schizophrenia. This, together with results from other types of studies, indicates the potential therapeutic value of developing drugs capable of selectively activating, inhibiting, or modulating GABA(B) receptor function.