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.

Epilepsy or epileptic syndromes affect more than 70 million people, often comorbid with autism spectrum disorders (ASD). Seizures are concerned as a factor for social regression in ASD. A stepwise experimental approach to this problem requires an animal model to provoke seizures and monitor subsequent behavior. We used rats of the Krushinsky–Molodkina (KM) strain as a validated inbred genetic model for human temporal lobe epilepsy, with recently described social deficiency and hypolocomotion. Generalized tonic-clonic seizures in KM rats are sound-triggered, thus being controlled events in drug-naïve animals. We studied whether seizure experience would aggravate contact deficits in these animals. Locomotor and contact parameters were registered in “the elevated plus maze”, “socially enriched open field”, and “social novelty/social preference tests” before and after sound-provoked seizures. The triple seizure provocations minimally affected the contact behavior. The lack of social drive in KM rats was not accompanied by a submissive phenotype, as tested in “the tube dominance test”, but featured with a poor contact repertoire. Here, we confirmed our previous findings on social deficits in KM rats. The contact deficiency was dissociated from hypolocomotion and anxiety and did not correlate with seizure experience. It was established that experience of rare, generalized tonic-clonic convulsions did not lead to an impending regress in contact motivation, as seen in an animal model of genetic epilepsy and comorbid social deficiency. One of the oldest animal models for epilepsy has a translational potential to study mechanisms of social behavioral deficits in future neurophysiological and pharmacological research.

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.

The inbred Krushinsky-Molodkina (KM) rat strain, characterized by latent genetic epilepsy, reduced social motivation, and a high propensity for freezing, is a promising model for translational research of social deficits in autism spectrum disorder (ASD). In clinical practice, social deficits often lead to social withdrawal and can be accompanied by aggression. It was unknown if KM rats exhibit such aggression during inescapable social encounters. We assessed intraspecific aggression in KM and control rats using the resident-intruder test, and autonomic nervous system responses were evaluated via heart rate variability analysis in a small separate cohort using a modified social-challenge paradigm that prevented direct physical contact. In the resident-intruder test, KM rats displayed significantly less aggression toward unfamiliar intruders than controls, exhibiting fewer attacks, fights, and competitive wins. Electrocardiographic analysis during the social preference test further revealed that the social challenge triggered parasympathetic, rather than sympathetic, nervous system activation in KM rats. Together, these findings indicate that social load in KM rats evokes a stress response, marked by a hypolocomotion and an atypical autonomic reaction. Conversely, control rats, which displayed a typical fight response to unfamiliar intruders, exhibited marked sympathetic activation during the sociability test. These findings suggest the KM strain may help model specific aspects of ASD-relevant social behavior alongside autonomic dysregulation.

Background/Objectives: The vibrotactile system, which is essential for guiding behavior in nocturnal rodents such as mice and rats, provides critical sensory input. To investigate the role of vibrotactile sensory inflow in neonatal locomotion, we used previsual rat pups that underwent bilateral vibrissectomy. Subsequently, their motor behavior was evaluated in an open field test. Methods: A total of 42 previsual pups from four litters were assigned to either bilateral vibrissectomy or sham surgery groups on postnatal days (PND) 9–12, with group allocation balanced across litters. Results: Open-field testing on PND 13 revealed that while vibrissectomy (VE) did not affect gross locomotor activity—such as distance traveled, speed, acceleration, or freezing episodes (all >0.05)—it significantly altered spatial behavior. To quantify spatial patterns of curvy tracks, we analyzed trajectorial compaction within the central zone, lacking the tactile guidance of the walls: trajectories were smoothed using virtual coatings scaled to the vibrissal length (16 mm). For each track, an individual linearized reference path was generated and subjected to identical smoothing. The compaction ratio—calculated as the coated area of the smoothed linearized reference divided by the coated area of the experimental track—was significantly greater in VE pups than in sham controls (p = 0.03). This effect was not attributable to differences in the path length traveled within the central zone. The increased compaction persisted when the smoothing scale was increased 2–3 fold (32–64 mm radii, approximating the pups’ mean body size), but not at smaller scales (2–4 mm). Conclusions: These results demonstrate that tactile input specifically modulates the spatial, rather than locomotor, components of nonvisual navigation. Consequently, the track compaction may serve as a sensitive marker for assessing vibrotactile function in developing laboratory rodents.

Background/Objectives:: The link between serotonergic modulation and depression is under debate; however, serotonin reuptake inhibitors (SRIs) are still the first-choice medicine in this condition. Disturbances in time perception are also reported in depression with one of the behavioral schedules used to study interval timing, differential-reinforcement-learning-of-low-rate, having been shown to have high predictive validity for an antidepressant effect. Here, we introduce an IntelliCage research protocol of an interval bisection task that allows more ecologically valid and less time-consuming rodent examination and provides an example of its use to confirm the previously reported acute effect of an SRI, clomipramine, on interval timing (increase in bisection point, D50). Methods: Wistar male rats (n = 25, five groups of 5–8) were trained in the IntelliCage to discriminate between short (1 s) and long (4 s) LED light stimuli by nose poking at the corresponding (left/right) side of the IntelliCage chamber to obtain a drink. When 80% of correct responses were reached, the intermediate durations of 1.7, 2.5, and 3.3 s were introduced. The number of left/right choices for each stimulus and interval timing parameters (bisection point, D50, and timing precision), derived from them, were compared after saline and clomipramine (7 mg/kg, i.p) intraperitoneal administration. Results: Rats successfully learned the task within about a week of training. The slightly increased D50 after clomipramine confirmed previous studies. Conclusions: The introduced protocol has potential to be applicable to preclinical research on depression and potentially other psychopathology, where time perception can be disturbed.