Behavioral alterations induced by post-weaning isolation rearing of rats are accompanied by reduced VGF/BDNF/TrkB signaling in the hippocampus.

Post-weaning social isolation has been shown to be a relevant animal model for studying the mechanisms underlying psychopathological states induced by early-life stressful experiences. Besides extensively studied brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) receptor, increasing attention is being given to a neuropeptide precursor VGF (non-acronymic). Several lines of evidence indicate an interplay between the neurotrophins and nitric oxide signaling. This study investigated the long-term consequences of post-weaning social isolation on behavior, VGF/BDNF/TrkB pathway and two isoforms of nitric oxide synthase (NOS) in the hippocampus and examined whether these effects were sex-specific. Male and female Sprague-Dawley rats were reared either in social isolation or social groups from postnatal day 21 for 9 weeks (n = 12-15/group and sex). Post-weaning social isolation induced impairments in sensorimotor gating and increased anxiety-like behavior in rats of both sexes. These behavioral alterations were accompanied by attenuated gene expression of VGF and TrkB receptor in the hippocampus. Isolation-induced reduction in VGF gene expression was more evident in male isolates. Similar changes were found in neuronal NOS (nNOS) gene expression with reduced mRNA levels in male isolates. Gene expression of BDNF and inducible NOS was not influenced by isolation rearing or sex. In addition, sex-specific patterns of VGF and nNOS gene expression in the hippocampus with higher mRNA levels in males than in females were revealed. The present study demonstrates a relationship between nNOS, VGF, BDNF, and TrkB confirming a link between nitric oxide and neurotrophins signaling pathways. Our findings indicate that long-term post-weaning social isolation alters signaling via VGF/BDNF/TrkB and nNOS that could interfere with neurodevelopmental processes which may contribute to pathological behavioral symptoms in adulthood. Future studies are needed to support this suggestion since the direct mechanistic link has not been approached in this study.

Inhibition of fatty-acid amide hydrolyse (FAAH) exerts cognitive improvements in male but not female rats.

OBJECTIVES: The endocannabinoid system is implicated in the regulation of various brain functions including cognition, memory, and behavior. It has been shown that inhibition of the endocannabinoid-degrading enzyme fatty acid amid hydrolase (FAAH) enhances the memory and learning in males. Given the fact that sexual dimorphism exists in the different components of the endocannabinoid system, the aim of this study was to test the hypothesis that cognition enhancing effect of the acute inhibition of FAAH by URB597 is gender dependent. METHODS: In the study, 32 adult male and female Sprague-Dawley rats were used. They were treated with a single intraperitoneal injection of FAAH inhibitor URB597 (0.3 mg/kg) or vehicle 40 min before behavioral testing. The novel object recognition test was used as a working memory task to assess cognitive performance. RESULTS: Neither the treatment nor the gender significantly affected the velocity, the total distance travelled and the time spent exploring the familiar object. The recognition of the object was influenced by both URB597 and gender. Male rats treated with URB597 displayed significantly increased novel object exploration compared to males treated with vehicle as well as to female rats treated with URB597. Single administration of URB597 significantly enhanced the recognition index in male, but not female rats. CONCLUSIONS: The results demonstrate that the positive effects of FAAH inhibition on the cognition are gender dependent. It is likely that male rats are more vulnerable to the modulation of the endocannabinoid system than female rats.

Effect of repeated electroconvulsive shock on plasma noradrenaline and adrenaline in man.

The concentration of noradrenaline (NA) and of adrenaline (A) in plasma was measured before and 3, 30 and 60 min after single and repeated electroconvulsive shocks (ECS). Single ECS resulted in an activation of the sympathoadrenal medullary system; however, after the treatment had been repeated 4 times there was evidence of a diminished response of the peripheral sympathetic nervous system in comparison to the response to the first ECS.