Effect of AMPA receptor modulators on hippocampal and cortical function

Attention has focused on drugs that modulate AMPA (alpha-amino-3-hydroxy-5- methyl-4-isoxazole proprionic acid) receptors because of their potential fo r enhancing memory and treating certain pathologies that involve glutamater gic neurotransmission. The aim of this study was to compare and contrast th e functionality of positive allosteric modulators of AMPA receptors in the hippocampus and medial prefrontal cortex. Electrically stimulated EPSPs (ex citatory postsynaptic potential) in the hippocampus were augmented by CX516 [(1-quinoxaline-6-ylcarbonyl)piperidine], aniracetam and 1-BCP [(1-(1,3-be nzodioxol-5-ylcarbonyl)piperidine] and not by cyclothiazide. Using grease g ap electrophysiology, it was found that the mode of application dramaticall y altered the effect of the modulators of AMPA-induced depolarization. When added simultaneously with AMPA, aniracetam, 1-BCP and CX516 augmented the response in the frontal cortex. However, in the hippocampus, only aniraceta m and cyclothiazide augmented the response when simultaneously added to AMP A. Therefore, in addition to regional variations, there appears to be diffe rences in modulator response dependent upon whether a response is generated endogenously or exogenously by AMPA. (C) 2000 Elsevier Science B.V. All ri ghts reserved.