Propofol suppresses intrinsic excitability and alters excitatory synaptic plasticity in ventral tegmental area dopamine neurons

Abstract

Propofol (2,6-diisopropylphenol) is a short-acting intravenous anesthetic used to induce and maintain general anesthesia. Beyond its anesthetic actions, propofol can produce rewarding subjective effects and has abuse potential. Because ventral tegmental area (VTA) dopamine neurons contribute to reward processing and arousal, we examined the effects of propofol on their intrinsic and excitatory synaptic properties using whole-cell patch-clamp recordings in acute rat midbrain slices. At 100 μM, propofol reduced evoked action-potential firing and increased rheobase in putative VTA dopamine neurons. It also reduced the AMPA/NMDA ratio of glutamatergic synaptic currents. A spike-timing-dependent plasticity (STDP) protocol induced sustained long-term potentiation (LTP) under control conditions, whereas the same protocol in the presence of 100 μM propofol produced persistent LTD-like synaptic depression. These findings show that, under acute slice conditions, propofol alters intrinsic excitability, excitatory synaptic balance, and activity-dependent synaptic plasticity in putative VTA dopamine neurons. Whether these cellular effects contribute to propofol-related arousal or reward behaviors remains to be tested.