Laboratory rats have excellent learning abilities and are often used in cognitive neuroscience research. The majority of rat studies are conducted on males, whereas females are usually overlooked. Here, we examined sex differences in behavior and tactile sensitivity in littermates during adulthood (5.8–7.6 months of age). We used a battery of behavioral tests, including the 2% sucrose preference test (positive motivation), a free-choice paradigm (T-maze, neutral situation), and associative fear-avoidance learning (negative motivation, aversive situation). Tactile perception was examined using the von Frey test (aversive situation). In two aversive situations (von Frey test and avoidance learning), females were examined during the diestrus stage of the estrous cycle, and ultrasonic vocalization was recorded in both sexes. It was found that (1) females, but not males, lost their body weight on the first day of the sucrose preference test, suggesting sex differences in their reaction to environmental novelty or in metabolic homeostasis; (2) the tactile threshold in females was lower than in males, and females less frequently emitted aversive ultrasonic calls; (3) in the avoidance learning task, around 26% of males (but no females) were not able to learn and experienced frizzing. Overall, the performance of associative fear-avoidance in males was worse than in females. In general, females demonstrated higher abilities of associative learning and less persistently emitted aversive ultrasonic calls.

In the present report, we evaluated adrenergic mechanisms of generalized spike-wave epileptic discharges (SWDs), which are the encephalographic hallmarks of idiopathic generalized epilepsies. SWDs link to a hyper-synchronization in the thalamocortical neuronal activity. We unclosed some alpha2-adrenergic mechanisms of sedation and provocation of SWDs in rats with spontaneous spike-wave epilepsy (WAG/Rij and Wistar) and in control non-epileptic rats (NEW) of both sexes. Dexmedetomidine (Dex) was a highly selective alpha-2 agonist (0.003–0.049 mg/kg, i.p.). Injections of Dex did not elicit de novo SWDs in non-epileptic rats. Dex can be used to disclose the latent form of spike-wave epilepsy. Subjects with long-lasting SWDs at baseline were at high risk of absence status after activation of alpha2- adrenergic receptors. We create the concept of alpha1- and alpha2-ARs regulation of SWDs via modulation of thalamocortical network activity. Dex induced the specific abnormal state favorable for SWDs—“alpha2 wakefulness”. Dex is regularly used in clinical practice. EEG examination in patients using low doses of Dex might help to diagnose the latent forms of absence epilepsy (or pathology of cortico-thalamo-cortical circuitry).

We examined sex differences in behavioral responses to fear-related learning through ultrasonic vocalization. Adult male and female rats of two inbred rat strains (WAG/Rij rats with genetic predisposition absence epilepsy, n = 25; and the minor substrain NEW with non-epileptic phenotype, n = 32) were examined in the two-way active avoidance task (50 trials). Three behavioral responses were defined: successful learning, unsuccessful learning, and freezing (motionless behavior). We found that males were more likely to experience freezing (40%) than females (3.7%). Females performed significantly better than males: 93% of females showed “successful learning”, while only 43.2% of males did. Long-lasting 22 kHz ultrasonic calls, so-called aversive ultrasonic vocalizations aUSVs, were recorded in 26% of females (only successful learners) and in 50% of males. The density of aUSVs in females was lower than in males. WAG/Rij males performed much poorer than the NEW males. In general, males, in contrast to females, showed significantly poorer avoidance learning, more frequently experienced freezing, and produced more aversive USVs. Males thus experienced a negative emotional state, rather than exhibiting poor cognitive abilities. Perhaps, WAG/Rij rats and a minor NEW substrain showed an increased emotionally in fear-related tasks, because they are prone to emotional disorders or emotional exhaustion. Sex differences in freezing and in aUSVs might result from the poorly understood neuromodulatory effects of the cholinergic system.

Electroencephalography (EEG) is a crucial tool for diagnosing absence epilepsy, a type of generalized epilepsy characterized by brief lapses of consciousness. Here, we used a Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat genetic model of absence epilepsy, in which spike-wave discharges (SWDs) manifested spontaneously and were linked to absence-like behavior. Conventionally, invasive electrocorticography (ECoG) with surgically implanted chronic electrodes has been used to confirm the absence epilepsy by the presence of SWDs in rats. However, this restricts the utilization of the same rat subject in multiple experiments. Therefore, there is a need for non-invasive EEG-based diagnostic tools in rats. This study introduces a novel, non-invasive EEG-based technique designed specifically for the rapid diagnosis of absence epilepsy. This approach is based on the sedative effect of xylazine and its unique capacity to induce SWDs. This approach was evaluated in a well-accepted genetic WAG/Rij rat model of absence epilepsy, including adult subjects of both sexes. Non-invasive EEG recording lasted 6 – 9 min. During the 6-min post-injection period, xylazine-induced SWDs closely resembled spontaneous SWDs in terms of the spike-wave morphology and frequency. The proposed non-invasive EEG-based technique is rapid, safe, inexpensive, and yields consistent results. Importantly, it can be repeated throughout a rat’s lifespan to assess the age-related progression of absence epilepsy.

Background: Absence epilepsy is a common pediatric neurological disorder characterized by brief seizures and lapses in awareness. The relationship between anxiety and absence epilepsy is multifaceted. This study aims to investigate neurobehavioral signs directly and indirectly related to anxiety and potential sex differences in aged WAG/Rij rats, a well-established animal model of absence epilepsy. Methods: A battery of behavioral tests was conducted to assess various aspects of neurobehavior, including anxiety (elevated plus maze), anhedonia (sucrose preference), social function, and associative learning (fear conditioning). Multidimensional metrics assessed cognition, motor function, and exploration strategies, prioritizing anxiety as a key influencing factor. Results: Electroencephalogram (EEG) phenotyping was used to identify epileptic and non-epileptic rats. Traditional anxiety measures in the elevated plus maze did not reveal significant differences between groups. However, the Anxiety Composite Index revealed higher autonomic reactivity in non-epileptic females. Cognitive assessments showed no epilepsy- or sex-related differences in overall learning performance. Females exhibited superior avoidance learning compared males. Among epileptic males, those with poor learning performance also displayed higher anxiety-avoidance scores. Rats with high anxiety levels showed enhanced socio-affective reactivity and passive coping, with no effect on exploratory learning. Conclusions: Our findings highlight the importance of sex-specific analyses and physiological measures in epilepsy research. Neurobehavioral comorbidities in WAG/Rij rat model are significantly influenced by anxiety-like behavioral phenotype. Enhanced phenotyping of rat models of absence epilepsy can improve its translational value in understanding epilepsy-associated psychiatric disorders.