Effects of propofol on hippocampal synaptic transmission in behaving rats

Background: The action of propofol has been studied in vitro and in vivo, b ut the effects of intravenously administered propofol on synaptic transmiss ion in freely behaving rats have not been studied before. Methods: Rats were implanted with recording electrodes in the dentate gyrus and with stimulation electrodes in the medial perforant path (MPP). Paired pulses at different interpulse intervals (IPIs) were delivered to the MPP, and average evoked potentials were recorded in the dentate gyrus before an d after a bolus of propofol (10 or 20 mg/kg administered intravenously) or control vehicle was injected via a femoral vein cannula. Because of the lay ered structure of the hippocampus, population excitatory postsynaptic poten tials and population spikes could be distinguished and analyzed. Results: Propofol has no significant effect on the population excitatory po stsynaptic potentials or population spike evoked by a single MPP stimulus p ulse. However, paired-pulse inhibition of the dentate population spikes was increased at IPI of 20 and 30 ms. Paired-pulse inhibition of the populatio n spike was most prominent when tail pinch response was lost (deep and mode rate anesthesia), but it persisted during light anesthesia. At 200 ms IPI, paired-pulse facilitation of population spikes was observed during moderate anesthesia in most rats. Conclusions: Tn freely behaving rats, intravenous propofol enhanced paired- pulse inhibition at < 50 ms IPI, likely by enhancing gamma-aminobutyric aci d, receptor-mediated inhibition, Propofol also increased paired-pulse facil itation at 200 ms IPI through an unknown mechanism, which may contribute to the neuroexcitatory effect of propofol.