GABA mimetics increase extracellular DOPAC (as measured by in vivo voltammetry) in the rat locus coeruleus

Previous studies have suggested that GABA exerts an indirect facilitatory influence on cerebral noradrenergic transmission that is likely to be mediated via GABA-ergic synapses involved in polysynaptic neuronal circuits controlling noradrenergic cell activity. In order to confirm these findings, we have studied the effect of GABA mimetics on extracellular DOPAC in the locus coeruleus (a reliable index of noradrenergic neuronal activity) of the rat through the use of in vivo voltammetry with carbon fibre electrodes. Systemic administration of progabide, its active metabolite SL 75.102, of depamide or muscimol increased the height of the DOPAC oxidation peak in the locus coeruleus; the effect of muscimol was antagonized by co-administration of bicuculline. Intra-locus coeruleus infusion of even a high concentration of muscimol (1 microgram) failed to alter extracellular DOPAC in this area. These results add further weight to the view that GABA exerts a facilitatory influence on noradrenergic neurons (via an increase in their cell firing) which is not effected at the level of their cell bodies or in the surrounding region.