Ameliorating Effects of Histamine H3 Receptor Antagonist E177 on Acute Pentylenetetrazole-Induced Memory Impairments in Rats

Behav Brain Res. 2021 Feb 21:113193. doi: 10.1016/j.bbr.2021.113193. Online ahead of print.ABSTRACTHistamine H3 receptors (H3Rs) are involved in several neuropsychiatric diseases including epilepsy. Therefore, the effects of H3R antagonist E177 (5 and 10 mg/kg, intraperitoneal (i.p.)) were evaluated on acute pentylenetetrazole (PTZ)-induced memory impairments, oxidative stress levels (glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)), various brain neurotransmitters (histamine (HA), acetylcholine (ACh), γ-aminobutyric acid (GABA)), and glutamate (Glu), acetylcholine esterase (AChE) activity, and c-fos protein expression in rats. E177 (5 and 10 mg/kg, i.p.) significantly prolonged step-through latency (STL) time in single-trial passive avoidance paradigm (STPAP), and shortened transfer latency time (TLT) in elevated plus maze paradigm (EPMP) (all P < 0.05). Moreover, E177 mitigated abnormal levels of AChE activity, ACh and HA (all P < 0.05), but failed to modify brain levels of GABA and Glu. Furthermore, E177 alleviated oxidative stress by significantly decreasing the elevated levels of MDA, and increasing the abnormally decreased level of GSH (all P < 0.05). Furthermore, E177 reduced elevated levels of hippocampal c-fos protein expression in PTZ-treated animals (all P < 0.05). The observed results propose the potential of H3R antagonist E177 with an added advantage of avoiding cognitive impairment, emphasizing the H3Rs as a...

Source: Behavioural Brain Research - February 24, 2021 Category: Neurology Authors: Alaa Alachkar Mohamed Lotfy Ernest Adeghate Dorota Łażewska Katarzyna Kie ć-Kononowicz Bassem Sadek Source Type: research