Long-term potentiation as an electrophysiological assay for morphine dependence and withdrawal in rats: An in vitro study

Using a long-term potentiation (LTP) method, we attempted to establish an electrophysiological assay for morphine dependence and withdrawal in rats in vitro. The field excitatory postsynaptic potential (fEPSP) and orthodromic population spikes (OPS) were recorded from stratums radiatum and pyramidale, respectively, of area CA1 following stimulation of Schaffer collaterals in control and morphine-dependent slices. To induce LTP, a 100 Hz primed-burst stimulation protocol was used. Although morphine exposure had excitatory effects on control slices, namely, an increase in the amplitude of primary population spikes (PSs) and appearance of extra PSs, slices taken from dependent rats demonstrated tolerance to morphine. LTP of the fEPSP was not changed in slices from dependent animals although dependent slices did show an enhanced OPS LTP compared to control ones, which was attenuated by morphine exposure. In the presence of morphine, naloxone caused a withdrawal phenomenon; apparent as a robust enhanced OPS LTP in dependent slices. So we propose morphine-naloxone withdrawn slices as a suitable in vitro withdrawal-like model. Such an in vitro preparation could provide a convenient practical experimental tool for examination of the probable molecular and cellular mechanisms involved in withdrawal states.