Paper Title
The Histamine H3R Antagonist E159mitigates Autismlike Behavioral Features in BTBR T+TF/J MICE

Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental brain disorder characterized by deficits in social interaction, repetitive stereotyped behaviors and restricted interests [1,2]. Brain histamine is involved in several neuropsychiatric disorders comorbid with ASD. Therefore, the palliative effects of the novel histamine H3 receptor (H3R) antagonist E159 with high H3R antagonist affinity and high in vitro selectivity profile towards H3Rs [3] on ASD-like behaviours in male BTBR T+tf/J mice as idiopathic model of ASD were assessed. Chronic systemic administration of E159 dose-dependently (2.5-10 mg/kg, i.p.)alleviated social impairments of tested BTBR mice, and significantly mitigated the repetitive/compulsive features of tested animals. Mnoreover, E-159 modulated disturbed anxiety levels, but failed to modulate hyperactivity parameters, whereas the reference drug donepezil (1 mg/kg) significantly restored the increased hyperactivity measures of tested mice. The E159-provided effects on social features were entirely reversed by co-administration of the H3R agonist (R)-α-methylhistamine (RAM) or the anticholinergic drug scopolamine (SCO, 0.3 mg/kg, i.p.), but not with H1 receptor antagonist pyrilamine (10 mg/kg, i.p.) nor the H2 receptor antagonist zolantidine (10 mg/kg, i.p.). These observations demonstrate that E159 alters histaminergic as well as cholinergic neurotransmissions crucial for alleviation of ASD-like features, albeit further in-vivo assessements on its effects on brain histamine and acetylcholine are still warranted. Keywords - Autistic spectrum disorder, BTBR mice, histamine H3 receptor antagonist, sociability, social novelty, stereotyped repetitive behavior, anxiety.