βCCM enhances retrieval of serial contextual but not of serial spatial memory in mice

The effects of inverse agonists of the γ-aminobutyric acid (GABA)/benzodiazepine receptors such as β-carboline-3-carboxylate (βCCM) on retrieval processes have not been studied extensively. This study investigates the effects in mice of an acute βCCM injection on retrieval of previously acquired serial discriminations, involving distinct contextual cues (Contextual Serial Discrimination, CSD) or identical cues (Serial Spatial Discrimination, SSD) in a four-hole board. Animals submitted to CSD were also evaluated for emotional reactivity in an elevated-plus maze. In both the CSD and the SSD tasks, mice were injected with saline before the learning session began. Twenty-four hours later, mice were replaced on the hole-board following a single dose of saline or βCCM (0.5 mg/kg or 1.5 mg/kg) injected 20 min before testing. The highest dose of βCCM improved performance of the first discrimination in the contextual task but not in the spatial task. Moreover, the higher dose of βCCM produced anxiety-like reactivity in an elevated-plus maze, and scores of ‘anxiety’ were positively correlated with memory scores. Overall, the data show that the βCCM enhancement of memory processes depends on(1) the cues associated with the to-be-remembered information; and (2) the emotional effects of the drug.