Frequency dependence of 5-HT autoreceptor function in rat dorsal raphe and suprachiasmatic nuclei studied using fast...

Fast cyclic voltammetry (FCV) at carbon fibre microelectrodes was used to monitor the time course of changes in extracellular concentration of endogenous 5-hydroxytryptamine ([5-HT]ex), in slices of rat brain containing either dorsal raphe nucleus (DRN) or suprachiasmatic nucleus (SCN). Five- or 20-pulse electrical stimulation trains were applied at frequencies between 5 and 500 Hz. [5-HT]ex was frequency and train length dependent, with maximum overflow in both sites at 100 Hz. Methiothepin (0.1 microM) caused a significant increase in [5-HT]ex when 5 pulses were applied at 5 Hz or when 20 pulses were applied at 10 or 20 Hz, but not at higher frequencies. When a single pseudo single pulse stimulation was used (5-pulse train at 100 Hz), methiothepin (0.1 microM) did not enhance [5-HT]ex in either the DRN or SCN; when 4 such pseudo single pulses were applied at 1 Hz methiothepin (0.1 microM) enhanced [5-HT]ex. A minimum period of stimulation of between 400 ms and 1 s was required for autoreceptor activation to occur in both regions. We conclude that [5-HT]ex can show a wide dynamic range of response to electrical stimulation, and that in both DRN and SCN it is subject to pulse-to-pulse regulation by presynaptic autoreceptors.