Impairment in the aversive memory of mice in the inhibitory avoidance task but not in the elevated plus maze through intra-amygdala injections of histamine

Abstract Rationale Evidence indicates that histamine (HA) modulates learning and memory in different types of behavioral tasks; however, the exact nature of this modulation and its mechanisms are controversial. Furthermore, emotions are able to influence memory processing in a crucial way through the involvement of the amygdala. Our research aims to contribute to the neurobiological body of knowledge on acquisition and retrieval of emotional memory via the histaminergic amygdaloid system in mice. Objectives The present study investigated whether exogenous HA infused into the amygdala differentially modulates the anxiety- and fear-related memory of mice assessed by unconditioned and conditioned tasks. Methods Over two consecutive days, animals received bilateral microinjections of either vehicle or HA (0.1, 0.5 and 1.0 μg by 0.1 μl/side volume) into the amygdala before behavioral tests were performed. Mice were examined under two paradigms: an exposure/re-exposure procedure in the elevated plus-maze (EPM) or in the inhibitory avoidance (IA) with electric foot shock trials 1 and 2 and retention test (without foot shock). Results Pre-test intra-amygdala microinjection of 0.5 μg HA induced anxiolytic-like responses, but none of the three doses interfered in mnemonic processing examined in the EPM. Concerning the IA task, step-through retention latencies increased in all groups compared with their respective trials, except in the animals microinjected with 0.5 or 1.0 μg HA before the retention test. Thus, HA caused statistically significant amnesia during the session repeated 24 h after training without drugs. Retention latency was not modified by microinjections of HA both pre-trial and pre-test or by pre-trial infusion in mice subjected to IA. Conclusions Our data indicate that the amygdaloid histaminergic system could modulate anxiety-related behaviors in the EPM and impair the retrieval process in fear conditioning with a strong aversive stimulus. These results contribute further evidence of the distinct histaminergic influence on different emotional pathways.