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

Abstract

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.

MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist‐like properties

“…Benzodiazepine inverse agonists also have been reported to enhance cognition (Venault et al, 1986;Lorez et al, 1988;Sarter et al, 1988a;Sarter & Stecker, 1989) and these compounds stimulate HACU after in vivo drug treatment (Miller & Chmielewski, 1990 reported for several potential nootropic agents (Shih & Pugsley, 1985;Spignoli et al, 1986;Nakahiro et al, 1988) suggesting that this may be a common mechanism for cognition enhancement among a diverse number of compounds. (Bowen et al, 1976;Arendt et al, 1983 Several studies have demonstrated that drugs with cognition enhancing potential can enhance LTP in the hippocampus (Olpe & Lynch, 1982;Ito et al, 1988;Tanaka et al, 1989;Pugliese et al, 1990). It has been suggested that inhibition of interneurones may underlie increased excitability in the hippocampus (Bilkey & Goddard, 1985 Moran et al (1992).…”

Modulating effect of the nootropic drug, piracetam on stress‐ and subsequent morphine‐induced prolactin secretion in male rats

“…The U-shaped dose-action curve of piracetam found in the present study is common among nootropics. In the literature, a considerable number of studies mention the fact that piracetam in lower doses exerts a significant effect while in higher doses the effect may either dissipate until it completely disappears (Satoh et al, 1986;Marchi et al, 1990;Pugliese et al, 1990;Pizzi et al, 1993) or reverse direction (Raiteri et al, 1992;Spignoli et al, 1986), resulting in a reversed dose-response curve or a U-or bell-shaped curve respectively.…”

“…Glutamate is the main neurotransmitter of excitatory cell signal processes and its release after cell depolarization has been shown to be potentiated by nootropics (Marchi et al, 1990). Moreover, nootropics enhance neurotransmission of the different types of glutamate receptors (Pugliese et al, 1990;Tang et al, 1991;Copani et al, 1992;Tsuzuki et al, 1992). Since several recent studies suggest that the EAA system is also involved in opioid action, both after acute immobilization stress (Tocco et al, 1991) and in tolerance and withdrawal conditions (Akaoka & Aston-Jones, 1991;Aghajanian et al, 1994), and since NMDA-antagonists can attenuate morphine-induced tolerance (Marek et al, 1991;Trujillo & Akil, 1991;Tiseo & Inturrisi, 1993), it is possible that it is through this EAA system that piracetam exerts its effects on opioid stress and tolerance.…”

“…oxiracetam, aniracetam, pramiracetam,...) do not possess a significant affinity for any known receptor binding site (for review see Gouliaev & Senning, 1994). It has been shown that nootropics can potentiate excitatory neurotransmission (Satoh et al, 1986;Marchi et al, 1990;Pugliese et al, 1990) and even slow desensitization of the excitatory receptors involved (Tang et al, 1991).…”

The Effects of Oxiracetam (CT-848) on Local Cerebral Glucose Utilization after Focal Cerebral Ischemia in Rats.

“…Thus, the effects of pyrrolidone deriva tives may be related to the enhancement of brain cholinergic mechanisms. In addition, ox iracetam and other pyrrolidone derivatives have been shown to augment hippocampal long-term potentiation in rats (6) and guinea pigs (7,8). These investigations suggest that pyrrolidone derivatives enhance cerebral func tion in normal brain and protect it in impaired brain.…”