Rat brain cholinergic, dopaminergic, noradrenergic and serotonergic neurons express GABAA receptors derived from the alpha3 subunit

In order to study the most abundant GABAA receptor subtypes expressed in cholinergic, dopaminergic, noradrenergic and serotonergic neurons (i.e., in neurons of the so-called "global" projection systems), we employed double-immunocytochemical techniques combining the labeling of GABAA receptor alpha1, alpha2 and alpha3 subunit with markers for these cells. Cholinergic neurons in the striatum, habenula, and pedunculo-pontine nucleus were immunonegative for the alpha1 subunit, and most were also alpha2-immunonegative. However, cholinergic neurons in the striatum, septum and pedunculo-pontine nucleus were alpha3 immunopositive. Dopaminergic neurons in the substantia nigra pars compacta were highly immunopositive for the alpha3, and noradrenergic neurons in the locus coeruleus were immunoreactive for the alpha3 and the alpha2-subunit; although neurons of these areas were negative for alpha1. Similarly, serotonergic neurons in raphe also showed a high level of labeling of alpha3, while there was a lack of immunoreactivity for the alpha1-subunit, and only some individual neurons were positive for the alpha2 subunit. As the presence of different alpha-subunits confers specific physiological and pharmacological properties to GABAA receptors, the abundance of receptors containing the alpha3 subunit (and the scarcity of receptor subtypes including the other alpha-subunits studied) may have important implications for the GABAergic regulation of brain "global" or "diffuse" projection systems.