Inhibition of locus coeruleus neurons by serotonin at high doses

Using brain slice and intracellular recording techniques, this study was conducted in the attempt to evaluate whether serotonin (5-HT) is able to directly influence neuronal activities of the locus coeruleus (LC). LC neurons in the brain slice preparation show spontaneous firing in the absence of synaptic input; neurons in this work had firing rates ranging from 0.18-3.6 Hz (mean = 1.18 +/- 0.26 Hz). Concentrations of 5-HT from 30 to 300 microM were used, which reversibly decreased the spontaneous firing rate in 30 out of 36 LC neurons tested. In testing those cells with more than one concentration, the effect was dose-dependent. For LC neurons which showed complete block of firing by 5-HT (300 microM), the latency to block was found to be directly related to the firing rate. In addition to the inhibition of spontaneous firing, 5-HT (300 microM) also caused a 0-5 mV (mean = 3.2 mV, n = 10) hyperpolarization associated with a 2.2-21% (mean = 11.5%, n = 10) decrease in input resistance. Lower concentrations of 5-HT (30-100 microM) did not produce any significant change in membrane potential or input resistance in neurons of the LC. The 5-HT receptor antagonist methysergide (10 microM) was tested in 6 cells. Methysergide antagonized the 5-HT-induced inhibition of firing, hyperpolarization and reduction in input resistance. We concluded that 5-HT has inhibitory actions at high doses when applied to LC neurons in the brain slice preparation. 5-HT's inhibitory effects on LC neurons appear to be mediated by 5-HT receptors since they are antagonized by methysergide.