Effect of etomidate on synaptic long-term potentiation in rat hippocampal slices

Objective To investigate the effect of etomidate on the synaptic long-term potentiation(LTP)in the CA1 region of rat hippocampal slices and the underlying mechanism.Methods Adult male SD rats aged 2 months weighing 200-250 g were anesthetized with ether and decapitated.Their brains were immediately removed and hippocampal slices(400 μm thick)were prepared.The slices were incubated in artificial cerebrospinal fluid(ACSF)at room temperature for at least 120 min before use.The experiment was performed in 2 parts.Part Ⅰforty-two slices were randomly divided into 6 groups(n=7 each):in group Ⅰ the slices were peffused with plain ACSF(control group)and in group Ⅱ,Ⅲ,Ⅳ,Ⅴ and Ⅵ the slices were perfused with ACSF containing etomidate 1,2,5,10 and 20 μmol/L respectively to determine the effect of different concentrations of etomidate on the amplitude of evoked population spikes (PSs). Part Ⅱ : another 84 slices were randomly divided into 12 groups ( n = 7 each ) : the slices were perfused with plain ACSF in group Ⅰ ( control group) ; with ACSF containing etomidate 1, 2, 5, 10 and 20 μmol/L respectively in group Ⅱ- Ⅵ ; with ACSF containing picrotoxin 50 μmol/L in group Ⅵ, or bicueulline 10 μmol/L in group Ⅷ or CGP35348 5 μmol/L in group Ⅸ or picrotoxin 50 μmol/L +etomidate 10 μmol/L (group Ⅹ) or bicuculline 10 μmol/L + etomidate I0 μmol/L (group Ⅺ ) or CGP35348 5 μmol/L + etomidate 10μmol/L (group Ⅻ ). Thirty minutes after PSs were recorded, high frequency stimulation(HFS) at 100 Hz was applied for 15 min to induce LTP. If the amplitude increased by ＞ 30% of the baseline value and maintained for more than 30 min, the induction of LIP was considered successful. Results In part Ⅰetomidate 5, 10 and 20 μmmol/L significantly decreased PS amplitude in group Ⅳ, Ⅴ and Ⅵ as compared with control group (Ⅰ ). In part Ⅱ PS amplitude was significantly increased by (52 ± 12) % after HFS as compared with the baseline value before HFS in control group ( Ⅰ ). The amplitude of PS after HFS was significantly decreased after HFS in group LTP Ⅲ, Ⅳ, Ⅴ and Ⅵ (etomidate 2, 5, 10, 20 μmol/L) as compared with group LTP Ⅰ (control group). The amplitude of PS was significantly increased after HFS as compared the baseline before HFS in picrotoxin, bicueulline and CGP35348 ( Ⅶ, Ⅷ, Ⅸ ) groups. The PS amplitude was significantly increased after HFS in picretoxin + etomidate grop and bicneullin + etomidate group as compared with the baseline before HFS and LTP etomidate 10 μmol/L group. Conclusion Etomidate can inhibit LTP by activating GABAA receptor in hippocampus, thus affecting learning and memory function. Key words: Etomidate ;  Hippocampus;  Synapses;  Long-term potentiation