Histamine H3 antagonist thioperamide dose-dependently enhances memory consolidation and reverses amnesia induced by dizocilpine or scopolamine in a one-trial inhibitory avoidance task in mice

In the literature, there is some evidence indicating that H3 histamine receptor antagonists, in particular thioperamide, can facilitate learning and memory retrieval in laboratory rodents. The present study aimed at verifying whether this also holds for memory consolidation, a phase of memory for which there is scarcity of convincing data on the effects of H3 receptor antagonists given systemically. To that end, memory consolidation was assessed in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the compounds being injected immediately after training (foot-shock) and performance measured 24 h later. More specifically, the following effects of thioperamide (1.25-20 mg/kg) were dose-dependently analysed: (1) its potential direct effects on memory consolidation; (2) its potential reversing effects on retrograde amnesia induced by the NMDA antagonist dizocilpine (MK-801, 0.5 mg/kg) and (3) its potential reversing effects on the well-known amnesia induced by the muscarinic antagonist scopolamine (0.25 mg/kg). We found that thioperamide exerted a dose-dependent facilitative effect on memory consolidation. Furthermore, the H3 receptor antagonist reversed scopolamine- and especially dizocilpine-induced amnesia. The results strongly support the view that the brain mechanisms of memory consolidation involve a functional interaction between the NMDA and the H3 sites. (C) 2004 Elsevier B.V. All rights reserved.