The prototypical histamine H3 receptor inverse agonist thioperamide improves multiple aspects of memory processing in an inhibitory avoidance task.

Numerous studies have found that histamine plays a major role in memory and that the histamine H3 receptor (H3R) inverse agonist thioperamide improves cognitive performance in various animal models. However, little is known about the stages of memory that are specifically affected by thioperamide. The purpose of the present study was to investigate the effects of thioperamide on acquisition, consolidation and retrieval processes in a one-trial inhibitory avoidance task in female C57BL/6J mice. In addition, potential state-dependency effects were studied by injecting thioperamide before the training and the test sessions in order to induce similar physiological states during acquisition and retrieval. Our results indicate that post-training systemic administration of thioperamide facilitated consolidation. Moreover, the administration of thioperamide before the training session had no effect on latency to enter the black compartment during training but enhanced memory during the retention test. The administration of thioperamide before the retention test also increased performance, which indicates that this compound ameliorates memory retrieval. Finally, when animals received thioperamide before the training session and before the retention test, the cognitive enhancing effects of thioperamide were not significantly changed. Together, our results show that thioperamide improves cognitive performance in an inhibitory avoidance task through actions on different memory stages. Furthermore, inducing a similar physiological state with thioperamide during acquisition and retrieval do not significantly affect cognitive enhancement. Our results suggest that the blockade of H3R can be helpful for the treatment of neuropsychiatric conditions characterized by deficits affecting several stages of memory processing.