5-HT containing terminals and fibres innervate the central autonomic area (CAA) of the thoracic spinal cord (Krukoff et al. 1985). Furthermore, within the CAA binding for 5-HT1 and 5-HT2 receptors is high (Marlier et al. 1991) and there is dense labelling for the 5-HT5A receptor (Doly et al. 2004). Therefore we sought to determine the effect of 5-HT application upon neurones in the CAA. Wistar rats (8-14 days old) or transgenic reporter GAD-65-GFP mice (8-21 days old) were terminally anaesthetised with urethane (2g/kg, i.p.) and transcardially perfused with ice cold 215 mM sucrose aCSF (Deuchars et al. 2005). The thoracic spinal cord was removed and transverse slices (300µm) prepared. Whole-cell patch clamp recordings (in current-clamp mode) were made from neurones within the CAA. Bath application of 5-HT onto neurones in the CAA elicited either depolarisations (+7.4±0.7mV, 20µM, n=15) or hyperpolarisations (-6.2±0.6mV, 20µM, n=26). Neurones that were hyperpolarised expressed a sag in the membrane potential in response to hyperpolarising current pulses (26/26) indicative of activating an Ih. Those that were depolarised expressed either an Ih (8/15), a delay in return to resting membrane potential indicative of activating an IA (5/15) or both an Ih and an IA (2/15). Both depolarising (n=7/7) and hyperpolarising (n=12/12) responses to 5-HT were mimicked by the 5-HT2 receptor agonist α-methyl-5HT (20µM). Depolarising responses persisted in the presence of 5-HT2B/2C antagonist SB200646 (5µM, n=3) but were subsequently blocked by 5-HT2A/2C antagonist ketanserin (1µM, n=3) indicating the involvement of 5-HT2A receptors. In preliminary recordings a GAD-65 neurone in the CAA was hyperpolarised by 5HT (20µM). This data demonstrates that 5-HT has both inhibitory and excitatory effects on neurones within the CAA. In the intermediolateral cell column (IML) 5-HT excites sympathetic preganglionic neurones (SPNs) suggesting a resultant increase in sympathetic outflow (Pickering et al. 1994). In the CAA 5-HT might act to increase sympathetic activity through one of two mechanisms; 1. Since some of the neurones that were excited by 5-HT had axon in the ventral horn this might suggest that these are SPNs, whilst others might be excitatory interneurones since direct excitation of these would result in an increase in sympathetic outflow. 2. An increase in sympathetic activity could also arise through the mechanism of disinhibition i.e. inhibition of inhibitory interneurones in the CAA which project to SPNs in the IML. This hypothesis is strengthened by the observation that a GAD-65+ve neurone was hyperpolarised by 5-HT and that a monosynaptic GABAergic pathway exists between neurones in the CAA and IML (Deuchars et al. 2005).