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Vol. 81, No. 2, 2008
Issue release date: January 2008
Pharmacology 2008;81:187–194

Repeated Administration of Histamine Improves Memory Retrieval of Inhibitory Avoidance by Lithium in Mice

Zarrindast M.R. · Parsaei L. · Ahmadi S.
aDepartment of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, bInstitute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, cInstitute for Cognitive Science Studies, dDepartment of Basic Sciences, Tehran North Unit, Azad University, Tehran, and eDepartment of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran

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The influence of repeated administration of histamine on lithium-induced state dependency has been investigated. A single-trial step-down inhibitory avoidance task was used to assess memory in adult male NMRI mice. Intraperitoneal (i.p.) administration of lithium (10 mg/kg), immediately after training (post-training), impaired inhibitory avoidance memory on the test day. Pre-test administration of lithium reversed amnesia induced by the drug given after training, with the maximum response at a dose of 10 mg/kg. Repeated intracerebroventricular (i.c.v.) administration of histamine (20 µg/mouse) for 3 consecutive days followed by 5 days of no drug treatment improved memory retrieval of inhibitory avoidance by a pre-test lower dose (5 mg/kg i.p.) of lithium. In contrast, 3 days of i.c.v. injections of both the histamine H1 receptor antagonist pyrilamine (40 µg/mouse) and the histamine H2 receptor antagonist ranitidine (6.25 and 12.5 µg/mouse) prevented the improving effect of pre-test lithium (10 mg/kg i.p.) on memory retrieval. The results suggest that the repeated administration of histaminergic agents may induce a sensitization which affects the memory impairment induced by lithium.

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