The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism.

摘要: Autistic spectrum disorder (ASD) is a neurodevelopmental characterized by impairment in social communication and restricted/repetitive behavior patterns or interests. Antagonists targeting histamine H3 receptor (H3R) are considered potential therapeutic agents for the management of different brain disorders, e.g., cognitive impairments. Therefore, effects subchronic treatment with potent selective H3R antagonist DL77 (5, 10, 15 mg/kg, i.p.) on sociability, novelty, anxiety, aggressive/repetitive male Tuck-Ordinary (TO) mice ASD-like behaviors induced prenatal exposure to valproic acid (VPA, 500 mg/kg, were evaluated using three-chamber test (TCT), marble burying (MBT), nestlet shredding (NST), elevated plus maze (EPM) test. The results showed that VPA-exposed exhibited significantly lower sociability novelty preference compared pretreated (10 i.p.). presented higher percentage buried marbles MBT shredded more NST control groups. However, animals reduced NST. On other hand, pretreatment failed restore disturbed anxiety levels hyperactivity observed EPM, whereas reference drug donepezil (DOZ, 1 mg/kg, palliated measures mice. Furthermore, modulated oxidative stress status increasing GSH decreasing MDA, it attenuated proinflammatory cytokines IL-1β, IL-6 TNF-α exacerbated lipopolysaccharide (LPS) challenge, mouse tissue. Taken together, these provide evidence modulation histaminergic neurotransmission, such as administration DL77, may serve an effective pharmacological target rescue animals, although further investigations necessary corroborate expand initial data.