Effect of the nootropic drug oxiracetam on field potentials of rat hippocampal slices.

1 The effect of the nootropic drug oxiracetam on hippocampal neurotransmission was investigated in the CAI region of the rat hippocampal slice in vitro by use of extracellular recordings. 2 Superfusion of oxiracetam (0.1-1001iM) produced a concentration-dependent, wash-resistant (>90 min), increase in initial slope and amplitude of the dendritic field excitatory postsynaptic potential (e.p.s.p.). This increase was maximal at a concentration of 1 YM (70%). 3 Input-output curves relating the initial slope to the amplitude of the afferent volley were significantly (P < 0.05) steeper and showed a greater maximal response in the presence of 1 gM oxiracetam than in control conditions. 4 Two trains of high frequency stimulation (100 Hz, 0.4 s, 5 min apart) delivered in the stratum radiatum 30min after washout of oxiracetam (1 yM) still elicited a long-term potentiation (LTP) of the field e.p.s.p. However, the absolute magnitude of the LTP produced did not differ from that obtained in untreated slices. 5 After induction and establishment of LTP, oxiracetam (1 yM) had a smaller (27%) and reversible effect on the evoked field e.p.s.p. 6 D-2-Amino-5-phosphonopentanoic acid (AP-5), at the same concentration (50pM) which in our conditions prevented the induction of LTP, blocked the action of 1 yM oxiracetam and strongly depressed the effect of higher concentrations of the nootropic drug. 7 It is concluded that oxiracetam provokes an enduring increase of neurotransmission in the CAl rat hippocampal region. This action appears to share some features with LTP as indicated by its persistence, sensitivity to AP-5 and lack of additivity with electrically-induced LTP.