βCCM but not physostigmine enhancement of memory retrieval depends on emotional processes in mice

Rationale: The effects of methyl beta-carboline-3-carboxylate (betaCCM, an inverse agonists of GABA/benzodiazepine receptors) or physostigmine (a cholinesterase inhibitor) on retrieval processes and relationships with anxiety have been only marginally studied. Objective: This study investigates in mice the effects of acute betaCCM or physostigmine injections on retrieval of previously acquired discriminations involving distinct contextual cues (serial contextual discrimination; SCD) in a four-hole-board. Animals submitted to SCD were also evaluated for emotional reactivity in an elevated-plus maze. Methods: Mice were injected before the learning session began with a saline solution. Twenty-four hours later, mice were replaced on the context of the initial acquisition and a single dose of saline or betaCCM (0.5 or 1.5 mg/kg) or physostigmine (0.05 and 1.0 mg/kg) was injected 20 min before testing. Results: The highest dose of either betaCCM or physostigmine improved performance of the first discrimination in the SCD task. The higher dose of betaCCM produced anxiety-like reactivity in the plus maze, and scores of "anxiety" were significantly correlated with memory scores; in contrast, memory performance of physostigmine-treated subjects were totally independent of emotional reactivity. Conclusions:These results show that, as opposed to physostigmine, betaCCM acts on retrieval processes specifically through its emotional component.