In clinical practice, epilepsy is often comorbid with the autism spectrum disorders (ASDs). This warrants a search of animal models to uncover putative overlapping neuronal mechanisms. The Krushinsky-Molodkina (KM) rat strain is one of the oldest inbred animal models for human convulsive epilepsies. We analyzed the behavioral response of adult seizure-naive KM males in three-chambered tests for social preference. We found that a presence of social stimuli (encaged unfamiliar Wistar rats of the same age and sex) evoked a reduced or reversed exploratory response in freely moving KM individuals. The epilepsy-prone rats demonstrated remarkably shortened bouts of social contacts and displayed less locomotion around the stranger rat-containing boxes, together with a pronounced freezing response. The decrease in social preference was not due to a general decrease in activity, since relative measures of activity, the index of sociability, were decreased, too. The susceptibility to audiogenic seizures was verified in the KM cohort but not seen in the control Wistar group. We propose the KM rat strain as a new animal model for comorbid ASD and epilepsy.

A popular model organism for studying neural and molecular mechanisms of behavior, the zebrafish ( Danio rerio ) displays a wide range of robust and quantifiable social phenotypes, including shoaling/schooling, social preference and learning, as well as aggression and mating behaviors. Zebrafish social behavior is influenced by various neurotransmitters and hormones (including serotonin, dopamine, isotocin, cortisol, and endocannabinoids) and can be modulated experimentally, including genetically and pharmacologically. Here, we summarize current knowledge on neurobiology and neuropharmacology of zebrafish social behavior, and discuss various effects of drugs and other manipulations that target this critical behavioral domain.

Objectives: Animal models of human diseases are commonly used in experimental research. Autism Spectrum Disorder (ASD) is characterized by reduced social motivation and often co-occurs with epilepsy, representing a distinct clinical subgroup. This study investigated social deficits in Krushinsky-Molodkina (KM) rats, which present with latent epilepsy and an autistic-like phenotype, by measuring ultrasonic communications during social interaction. Methods: The three-chamber test for social preference/novelty, accompanied by registration of ultrasonic vocalizations (USVs), was conducted in 12 KM and 12 control Wistar rats. For analysis, each individual vocalization trajectory was mapped and the results were derived from aggregating the individual data. To assess potential anhedonia, sucrose preference was tested in a separate group (10 KM and 20 Wistar rats) by measuring the consumption of 1% sucrose and water in individual rats over a 24-h period. All animals used were seizure-naive males, aged 4–6 months. Results: A longer duration of aversive USV calls was registered during the sociability tests in KM rats (p < 0.05, compared with controls). The majority (p < 0.05) of aversive USVs occurred when KM rats distanced themselves from the social stimuli, and the duration of these calls showed a positive correlation with freezing behavior (Spearman coefficient Rs = 0.68, p < 0.05). Reduced sucrose preference was not observed in KM rats; instead, an increase in daytime sucrose consumption was noted. Conclusions: KM rats exhibit negative emotional states in sociability tests, as evidenced by enhanced aversive vocalizations and distancing behavior. The social aversion observed in KM rats is not associated with anhedonia.

Background/Objectives: Chronic stress and neuroinflammation (promoted by micro- and astroglia) represent key factors in affective pathogenesis. Complementing rodent models, zebrafish (Danio rerio) are widely used in experimental modeling of affective disorders. Here, we examined the effects of chronic treatment with two distinct anti-inflammatory drugs, minocycline and nimesulide, on behavior and neuroinflammation-related biomarker genes in the zebrafish chronic unpredictable stress (CUS) model. Methods: Following two-week CUS with or without drug treatment, fish were assessed using the novel tank test for anxiety-like behavior, and the zebrafish tail immobilization (ZTI) test for depression-like behavior. Results: A 14-day treatment with minocycline (50 mg/L) reduced general motor activity and brain expression of both pro-inflammatory (nos2a) and anti-inflammatory (arg1) microglial biomarker genes, as well as upregulated the anti-inflammatory astrocytic marker s100a10. In CUS-exposed fish, this treatment attenuated depression-like ZTI immobility behavior and downregulated both pro-inflammatory (nos2a, cox2) and anti-inflammatory (arg1, ptx) glial biomarkers compared to the stress-only control. In contrast, one-week nimesulide treatment during CUS produced an anxiolytic-like effect and normalized the expression of stress-induced pro-inflammatory glial biomarkers cox2 and il1β. Conclusions: Overall, our findings suggest that the two anti-inflammatory drugs tested modulate behavioral and molecular responses to chronic stress in zebrafish, with minocycline demonstrating broader anti-neuroinflammatory and antidepressant-like effects, and nimesulide exhibiting more specific anxiolytic-like properties in this model.

Cortical immature neurons (cINs) represent a unique population of prenatally generated, non-dividing neurons that maintain an immature phenotype, characterized by doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) expression, into adulthood. Unlike canonical adult neurogenesis involving continuous neuron generation from stem cell niches, cINs constitute a distinct form of structural plasticity termed “neurogenesis without division”. This review comprehensively examines the molecular markers, morphological diversity, developmental origins, and maturation trajectories of cINs across species. We highlight the striking inverse interspecies relationship between cIN abundance and canonical adult neurogenesis, reflecting distinct biophysical and structural shifts in neural plasticity mechanisms across mammalian lineages. Furthermore, we discuss factors modulating cIN phenotype, including neurotransmitter systems, stress, sensory experience, and aging. Clinical evidence implicating cIN alterations in temporal lobe epilepsy, traumatic brain injury, and stroke is evaluated, revealing potential roles in both pathological circuit remodeling and endogenous repair. Critical gaps remain regarding the molecular programs maintaining immaturity, differentiation triggers, and the functional consequences of circuit integration. Understanding cIN biology offers new perspectives on cortical plasticity and may inform therapeutic strategies targeting endogenous cellular reserves for brain repair.