Bidirectional modulation of cortical acetylcholine efflux by infusion of benzodiazepine receptor ligands into the basal forebrain

Abstract

In a previous in vivo microdialysis study in rats, it was found that cortical acetylcholine (ACh) efflux was reliably increased by a multimodal appetitive stimulus (onset of darkness with presentation of palatable food). Furthermore, this stimulated ACh efflux was significantly enhanced by systemic administration of a benzodiazepine receptor (BZR) weak inverse agonist and significantly reduced by a BZR full agonist. These effects contrasted with the minimal effects of BZR ligands on basal cortical ACh efflux in resting animals. The aim of the present study was to determine whether this modulation of stimulated cortical ACh efflux by BZR ligands was mediated within the basal forebrain. ACh efflux, measured with in vivo microdialysis, was stimulated by onset of darkness, an event which predicted delivery of palatable food. The BZR full inverse agonist, β-CCM (3.0 μg/hemisphere) or the full agonist chlordiazepoxide (40.0 μg/hemisphere) was infused into the basal forebrain just prior to the darkness/food stimulus. Similar to previous results with systemic administration, the BZR full inverse agonist enhanced, while the full agonist reduced, stimulated cortical ACh efflux. These results demonstrate that the action of BZR ligands in the basal forebrain is sufficient for their modulation of cortical ACh release.