SEROTONIN UPTAKE BLOCKERS INHIBIT THE FIRING OF PRESUMED SEROTONERGIC DORSAL RAPHE NEURONS INVITRO

Some antidepressant drugs are potent inhibitors of neuronal uptake of serotonin. In vivo, these compounds inhibit serotonergic dorsal raphe neuronal firing rates, presumably through increased stimulation of 5-HT1a autoreceptors. We recorded from electrophysiologically identified serotonergic dorsal raphe neurons in rat brain slices and determined the effects of five serotonin uptake blockers on the firing rates of these units in vitro. Each drug decreased the neuronal firing rates in a concentration-dependent manner. IC50 values derived from concentration-response curves are: fluvoxamine, 0.8-mu-M; sertraline, 1.1-mu-M; imipramine, 2.7-mu-M; chlorimipramine, 2.8-mu-M; and fluoxetine, 4.2-mu-M. Exposure of brain slices to 10-mu-M tetrabenazine, a serotonin depleting agent, prior to treatment with serotonin uptake blockers resulted in a rightward shift of the concentration-response curve. In vitro single unit recording allows: 1) direct comparison with neurochemical data obtained in vitro; 2) access to tissue bypassing blood brain barrier and liver enzymes; 3) quick wash out of drug from tissue; and 4) ability to record from single units over long periods (hours). This in vitro test provides a fast, simple means of determining neurophysiological effects of potential antidepressant drugs on the serotonin system.