The influence of long-term housing in enriched environment on behavior of normal rats and subjected to neonatal pro-inflammatory challenge

It is well known that neonatal pro-inflammatory challenge (NPC) acquire a predisposition to the development of a number of neuropsychiatric diseases: depression, anxiety disorders, autism, attention deficit hyperactivity disorder. Symptoms of these diseases can manifest themselves in adulthood and adolescent after repeated exposure to negative influences. Preventing the development of the negative consequences of NPC is one of the main tasks for researchers. The exposure to an enriched environment (EE) was shown to have anxiolytic, anti-depressive, and pro-cognitive effects. The present work was aimed to investigate the effects of the long-term EE on anxious-depressive and conditioned fear behavior in normal male and female rats and subjected to NPC. The NPC was induced by subcutaneous administration of lipopolysaccharide (LPS, 50 μg/kg) on 3d and 5th PNDs. The control animals received saline (SAL). The rats were placed in the EE from 25 to 120 PND. Animals housed in the standard conditions (STAND) served as controls. In adult female and male rats of the STAND groups, LPS did not affect the anxiety, depressive-like behavior and conditioned fear. The EE increased motor and search activity in males and females. In the open field, the EE reduced anxiety in males of the SAL and LPS groups and in females of SAL groups compared to the STAND housed animals. In the elevated plus maze, the EE decreased anxiety only in males of the SAL group. In the sucrose preference test, the EE did not change sucrose consumption in males and females of SAL and LPS groups, while, in the forced swimming test, the EE reduced depressive-like behavior in females of both SAL and LPS groups. The enrichment decreased the contextual conditioned fear in male and female of SAL groups, but not of the LPS group, and did not affect the cue conditioned fear. The corticosterone reactivity to the forced swimming stress increased in males of the EE groups. The basal level of IL-1beta in blood serum decreased in males of the SAL-EE group. Thus, the EE reduced anxiety in males, depressive-like behavior in females, and contextual conditioned fear in males and females compared to the STAND housed animals. Although the NPC did not affect these behaviors in the STAND groups, LPS prevented the beneficial EE effects on anxiety and conditioned fear. The opposing effects of LPS were dependent on sex and type of testing

Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats

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