Dissociation between the attentional effects of infusions of a benzodiazepine receptor agonist and an inverse agonist into the basal forebrain.

The effects of infusions of the benzodiazepine receptor (BZR) full agonist chlordiazepoxide (CDP) or the full inverse agonist beta-CCM into the basal forebrain on behavioral vigilance were tested. Vigilance was measured by using a previously characterized task that requires the animals to discriminate between visual signals of variable length and non-signal events. Measures of performance included hits, misses, correct rejections, false alarms, side bias, and errors of omission. Following the infusion of saline (0.5 microliters/hemisphere), the relative number of hits varied with signal length. In response to shorter signals, the number of hits decreased over time, indicating a vigilance decrement. Infusions of CDP (20, 40 micrograms/hemisphere) initially decreased the relative number of hits in response to shorter signals and, later in the course of the test sessions, to longer signals as well. CDP did not affect the relative number of correct rejections. In contrast, infusions of the inverse agonist beta-CCM (1.5, 3.0 micrograms/hemisphere) did not affect the relative number of hits but decreased the relative number of correct rejections (i.e., increased the number of false alarms). These data suggest that the basal forebrain mediates the attentional effects of BZR ligands. As systemic or intrabasalis administration of BZR agonists and inverse agonists was previously demonstrated to decrease and augment, respectively, activated cortical acetylcholine (ACh) efflux, their effects on behavioral vigilance are hypothesized to be mediated via their effects on cortical ACh.