Abstract

Synchronous hippocampal electroencephalographic activity occurring in a frequency range of 3 to12 Hz (i.e., hippocampal θ rhythm) has been associated with mnemonic processes in vivo. However, this link is tenuous and θ rhythm may be secondary to processes that underlie mnemonic function. If θ rhythm is associated with mnemonic or cognitive function, cognition-enhancing drugs should enhance θ rhythm regardless of their primary biological target. In the current study, we evaluated several drugs that were shown to have cognition-enhancing properties in preclinical behavioral models and that vary with respect to their primary biological target: 1) the nootropic piracetam (250 and 500 mg/kg); 2) the small-conductance calcium-activated potassium-channel blocker apamin (0.1 and 0.4 mg/kg); and 3) the acetylcholinesterase inhibitor donepezil (0.1–10.0 mg/kg). All of the cognition-enhancing drugs produced dose-dependent increases in hippocampal θ rhythm amplitude elicited by stimulation of the brainstem reticular formation at doses that did not affect peak θ frequency in the urethane-anesthetized rat. These increases were reversed by the muscarinic receptor antagonist scopolamine, suggesting a common final cholinergic action of these compounds. The use-dependentN-methyl-d-aspartate antagonist dizocilipine maleate and scopolamine reduced θ amplitude (both) and frequency (dizocilipine maleate only). These data demonstrate that hippocampal θ rhythm is sensitive to cognition-modulating compounds, suggesting that θ rhythm may be closely associated with cognitive function.