To study the effects of acute and repeated injections of nootropics and to learn how glutamate receptors might be involved in their mediation, the frequency spectra of cortical and hippocampal electroencephalogram (EEG) were analyzed in non-narcotized rats subcutaneously injected repeatedly with Piracetam (400 mg/kg) or its analogue, Noopept (0.2 mg/kg), after intracerebroventricular infusions of saline (5 μl) or the antagonists of NMDA and quisqualate/AMPA receptors: CPP (0.1 nmol) and GDEE (1 μmol), respectively. Piracetam increased alpha/beta1 EEG activity in the left frontal cortex, and alpha activity in both the right cortex and hippocampus, with a 10-min latency and 40-min duration. Noopept increased alpha/beta1 activity, with 30-min latency and 40-min duration in all brain areas. CPP pretreatment eliminated Piracetam EEG effects; reduced Noopept effects in the cortex and completely suppressed them in the hippocampus. After four injections of Piracetam, EEG effects were very small in the cortex, and completely lacking in the hippocampus, while GDEE pretreatment partially recovered them. The effect of Noopept in the alpha/beta1 ranges was replaced by increased beta2 activity after the eighth injection, while no effects were observed after the ninth one. GDEE pretreatment restored the effect of Noopept in the beta2 frequency range. These results demonstrate similarities in EEG effects and their mediatory mechanisms for Piracetam and its much more effective analogue, Noopept. Activation of NMDA receptors is involved in the effects of a single injection of the nootropics, whereas activation of quisqualate/AMPA receptors is associated with the decrease in their efficacy after repeated use.