The Histamine H3 Receptor Antagonist E159 Reverses Memory Deficits Induced by Dizocilpine in Passive Avoidance and Novel Object Recognition Paradigm in Rats.

The involvement of histamine H3 receptors (H3Rs) in memory is well known, and the potential of H3R antagonists in therapeutic management of neuropsychiatric diseases, e.g., Alzheimer disease (AD) is well established. Therefore, the effects of histamine H3 receptor (H3R) antagonist E159 (2.5-10 mg/kg, i.p.) in adult male rats on dizocilpine (DIZ)-induced memory deficits were studied in passive avoidance paradigm (PAP) and in novel object recognition (NOR) using pitolisant (PIT) and donepezil (DOZ) as standard drugs. Upon acute systemic pretreatment of E159 at three different doses, namely 2.5, 5, and 10 mg/kg, i.p., 2.5 and 5 but not 10 mg/kg of E159 counteracted the DIZ (0.1 mg)-induced memory deficits, and this E159 (2.5 mg)-elicited memory-improving effects in DIZ-induced amnesic model were moderately abrogated after acute systemic administration of scopolamine (SCO), H2R antagonist zolantidine (ZOL), but not with H1R antagonist pyrilamine to the animals. Moreover, the observed memory-enhancing effects of E159 (2.5 mg/kg, i.p.) were strongly abrogated when animals were administered with a combination of SCO and ZOL. Furthermore, the E159 (2.5 mg)-provided significant memory-improving effect of in DIZ-induced short-term memory (STM) impairment in NOR was comparable to the DOZ-provided memory-enhancing effect, and was abolished when animals were injected with the CNS-penetrant histamine H3R agonist