Abstract
In vivo microdialysis techniques were used to determine the ability of glutamate receptors within the nucleus accumbens to trans-synaptically modulate the basal forebrain cortical cholinergic system. Rats were implanted with a dialysis probe in the medial prefrontal cortex to measure changes in cortical acetylcholine efflux and in the ipsilateral nucleus accumbens to locally manipulate glutamate receptor activity. Intra-accumbens perfusion of the broad spectrum ionotropic glutamate receptor antagonist kynurentate (1.0, 5.0 mm) led to a dose-dependent increase (maximum of 200%) in cortical acetylcholine efflux. This stimulated efflux was reproduced with the intra-accumbens perfusion of the AMPA/kainate antagonist DNQX (0.1, 0.25, 2.5 mm; maximum increase of 200%) or the NMDA antagonist D-CPP (10.0, 100.0, 200 micro M; maximum increase of 400%). These results reveal a significant glutamatergic tone within the accumbens of awake rats and support the hypothesis that accumbens efferents to basal forebrain modulate the excitability of the basal forebrain cortical cholinergic system.
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