Neurodegenerative processes are likely to be due at least in part by the release of pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF)α. Evidence is now emerging that these cytokines may act as immuno-transmitters affecting dopamine and serotonin transmission (Allan & Rothwell, 2001). Application of IL-1 can modulate K -and NMDA-evoked dopamine release in the nucleus accumbens (Song et al. 1999). Also TNFα has been shown to potentiate striatal dopamine uptake into synaptosomes (Cho et al. 1999). However there are conflicting reports for the effects of TNFα on regional brain neurotransmitters. Using the technique of fast cyclic voltammetry (FCV; Kruk & O’Connor, 1995), we have investigated in real time the release and reuptake kinetics of dopamine in the rat striatum in the presence and absence of TNFα. Rats were humanely killed and changes in the extracellular concentration of dopamine evoked by electrical stimulation of rat brain slices containing the caudate putamen were monitored using FCV. In FCV, a triphasic voltage ramp is applied to the slice, and the resultant current is measured using a carbon fibre electrode. Dopamine is known to oxidise at 610 mV and the current measured is proportional to the concentration of dopamine present in the extracellular fluid. Single pulse stimulation (0.1 ms; 10 V) and 4 pulses at 0.5 Hz were applied once every 5 min over a 3 hr period. Data are expressed as mean±sem and analysed using Students unpaired t-test. Perfusion of TNFα (5.0 ng/ml; 380 pM) for 2 hr had no significant effect on single pulse release or reuptake kinetics (control single pulse peak release was 0.30±0.03 μM versus 0.37±0.04 μM 2 hr post TNFα; P>0.05, n=4). During the 0.5 Hz stimulation protocol, no effect on the ratio of the 3rd stimulation to the 1st stimulation was observed (0.53±0.08 control, versus 0.49±0.03 in TNFα treated slices; P>0.05; n=4). This indicates that D₂ autoreceptors were not affected by TNFα. These results show that acute exogenous application of pathophysiological concentrations of TNFα does not affect dopamine release, reuptake, or D₂ autoreceptors kinetics. These studies will provide valuable information towards our understanding of the mechanisms of action of TNFα on dopamine release.