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Antihistaminic drugs are widely used clinically and have long been primarily known for their use to treat severe allergic conditions caused by histamine release. Antihistaminic drugs also exert central nervous system (CNS) effects, acting as anxiolytics, hypnotics, and neuroleptics. However, these drugs also have multiple serious neuropharmacological side-effects, inducing delirium, hyperarousal, disorganized behavior, and hallucinations. Due to their robust CNS effects, antihistamines are also increasingly abused, with occasional overdoses and life-threatening toxicity. Here, we discuss chemical and neuropharmacological aspects of antihistaminic drugs in both human and animal (experimental) models and outline their current societal and mental health importance as neuroactive substances.

Highly prevalent in laboratory rodents, 'social' hetero-grooming behavior is translationally relevant to modeling a wide range of neuropsychiatric disorders. Here, we comprehensively evaluated all known to date mouse genes linked to aberrant hetero-grooming phenotype, and applied bioinformatics tools to construct a network of their established protein-protein interactions (PPI). We next identified several distinct molecular clusters within this complex network, including neuronal differentiation, cytoskeletal, WNT-signaling and synapsins-associated pathways. Using additional bioinformatics analyses, we further identified 'central' (hub) proteins within these molecular clusters, likely key for mouse hetero-grooming behavior. Overall, a more comprehensive characterization of intricate molecular pathways linked to aberrant rodent grooming may markedly advance our understanding of underlying cellular mechanisms and related neurological disorders, eventually helping discover novel targets for their pharmacological or gene therapy interventions., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Rodent self-grooming is an important complex behavior, and its deficits are translationally relevant to a wide range of neuropsychiatric disorders. Here, we analyzed a comprehensive dataset of 227 genes whose mutations are known to evoke aberrant self-grooming in mice. Using these genes, we constructed the network of their established protein-protein interactions (PPI), yielding several distinct molecular clusters related to postsynaptic density, the Wnt signaling, transcription factors, neuronal cell cycle, NOS neurotransmission, microtubule regulation, neuronal differentiation/trafficking, neurodevelopment and mitochondrial function. Utilizing further bioinformatics analyses, we also identified novel central ('hub') proteins within these clusters, whose genes may also be implicated in aberrant self-grooming and other repetitive behaviors in general. Untangling complex molecular pathways of this important behavior using in silico approaches contributes to our understanding of related neurological disorders, and may suggest novel potential targets for their pharmacological or gene therapy., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)