Social isolation and social support at adulthood affect epigenetic mechanisms, brain-derived neurotrophic factor levels and behavior of chronically stressed rats.

Epigenetic modulation of brain-derived neurotrophic factor (BDNF) provides one possible explanation for the dysfunctions induced by stress, such as psychiatric disorders and cognitive decline. Interestingly, social support can be protective against some of these effects, but the mechanisms of social buffering are poorly understood. Conversely, early isolation exacerbates the responses to stressors, although its effects in adulthood remain unclear. This study investigated the effects of social isolation and social buffering on hippocampal epigenetic mechanisms, BDNF levels and behavioral responses of chronically stressed young adult rats. Male Wistar rats (3 months) were assigned to accompanied (paired) or isolated housing. After one-month half of each group was submitted to a chronic unpredictable stress (CUS) protocol for 18 days. Among accompanied animals, only one was exposed to stress. Behavioral analysis encompassed the Open field, plus maze and inhibitory avoidance tasks. Hippocampal H3K9 and H4K12 acetylation, HDAC5 expression and BDNF levels were evaluated. Isolated housing increased HDAC5 expression, decreased H3K9 and H4K12 acetylation, reduced BDNF levels, and impaired long-term memory. Stress affected weight gain, induced anxiety-like behavior and decreased AcK9H3 levels. Interactions between housing conditions and social stress were seen only for HDAC5 expression, which showed a further increase in the isolated + CUS group but remained constant in accompanied animals. In conclusion, social isolation at adulthood induced epigenetic alterations and exacerbated the effects of chronic stress on HDAC5. Notwithstanding, social support counteracted the adverse effects of stress on HDAC5 expression.

Differential effects of low and high doses of topiramate on consolidation and retrieval of novel object recognition memory in rats.

Topiramate is a new antiepileptic drug proposed to facilitate synaptic inhibition and block excitatory receptors. However, little is known about the effects of topiramate on memory. In the first experiment, intraperitoneal injection of topiramate at doses of 10.0 and 100.0 mg/kg, immediately after training, induced a deficit in short-term memory (STM) of a novel object recognition (NOR) task tested 1.5 hours after training in rats. In a long-term memory (LTM) test given to the same rats 24 hours after training, topiramate 0.1mg/kg enhanced, whereas 10.0 and 100.0 mg/kg impaired, NOR retention. In the second experiment, administration of topiramate 0.01 and 0.10 mg/kg 1 hour prior to the LTM retention test improved NOR retention, whereas 10.0 and 100.0 mg/kg produced retrieval deficits. The results indicate that low doses of topiramate improve, whereas high doses impair, consolidation and retrieval of recognition memory in rats.