Monoamine modulation of tonic GABAA inhibition

In recent years, it has become evident that many neurotransmitters and endogenous ligands differentially modulate synaptic gamma-aminobutyric acid type A receptors (sGABA(A)Rs) and extrasynaptic GABA(A)R (eGABA(A)Rs). In this mini-review, we will summarize the available evidence on the ability of the monoamines serotonin (5-HT), noradrenaline (NA), and, in particular, dopamine (DA) to alter the functional response of eGABA(A) Rs, thus either increasing or decreasing tonic GABA(A) inhibition. Although this field of research is still in its infancy, it has already been demonstrated that eGABA(A) Rs show a nucleus-selective and neuronal-type-selective regulation by monoamines in a way that differs from that of sGABA(A) Rs. Further work will undoubtedly advance our knowledge of the intricate talk between monoamines and eGABA(A) R and may ultimately provide new leads for the treatment of neurological and neuropsychiatric disorders, where alteration in GABA(A) R function is one of the underlying causes.