Nootropic compound L-pyroglutamyl-D-alanine-amide restores hippocampal long-term potentiation impaired by exposure to ethanol in rats.

The characteristics of long-term potentiation (LTP) in the hippocampus of rats prenatally exposed to ethanol and treated postnatally with nootropic compounds L-pyroglutamyl-D-alanine-amide (L-pGlu-D-AlaNH2, PGA) or piracetam were studied using in vitro slice preparations. LTP was induced in the CA1 region by the orthodromic stimulation of the stratum radiatum with one train of 100 pulses (100 Hz, 1 s). The probability of LTP development in the hippocampus of young rats was significantly reduced by prenatal exposure to alcohol. This plasticity deficit was completely reversed by daily injections of PGA, 1 mg/kg for 12 days (8-19 days of postnatal development) but not of piracetam, 100 mg/kg. PGA (0.5 microM) also prevented the inhibition of LTP development in hippocampal slices perfused with ethanol, 20 or 50 mM. The data indicate that PGA effectively restores synaptic plasticity after both prenatal and acute exposure to ethanol and suggest that impaired LTP may be a useful model for studying the mechanisms of action of nootropic compounds.