Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex

Abstract

a b s t r a c tAdolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peripubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific.

CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors

“…Recently, a study in rhesus monkeys has shown that single nucleotide polymorphisms in the Crhr1 gene affect both anxiety temperament and metabolic activity in the anterior hippocampus and amygdala (Rogers et al, 2013). Interestingly, our previous data have also highlighted changes in the metabolic activity of hippocampus and amygdala in peripubertally stressed rats (Toledo-Rodriguez et al, 2012;Marquez et al, 2013). Furthermore, increasing CRH drive occurring specifically in the central amygdala through lentiviral-induced neuropeptide overexpression was also found to enhance anxiety-like (Flandreau et al, 2012) and depression-like (Keen-Rhinehart et al, 2009) behaviors in rats.…”

“…The peripubertal period is a biological transitional phase involving adaptations in hormonal systems and neural circuits, including those related to stress and the development of emotionality (Spear, 2009;Romeo, 2010). In our lab, exposure of rats to stressful experiences (e.g., synthetic fox odor and exposure to an elevated platform) on scattered days during the peripuberty period (P28eP30, P34, P36, P40 and P42) was found to induce long-lasting effects on anxiety and stress-coping behaviors, including deficits in social behaviors (Toledo-Rodriguez and Sandi, 2011;Cordero et al, 2012;Marquez et al, 2013), as well as changes in metabolic responses in limbic brain regions including the hippocampus and the amygdala (Toledo-Rodriguez et al, 2012;Marquez et al, 2013). Here, we sought to investigate whether peripuberty stress would lead to alterations in the CRH system in limbic areas and whether pharmacological treatment with a CRHR1 antagonist during the immediate post-stress developmental period (i.e., adolescence) would reverse the long-term behavioral consequences of peripuberty stress.…”

Individual differences in recovery from traumatic fear

“…An important extension to this approach has been to measure patterns of endogenous activation, simultaneously in multiple brain regions, associated with population and/or strain differences in extinction. Neuronal correlates of individual differences in extinction have been examined using imaging techniques, including metabolic mapping (via 2-deoxyglucose uptake [27]) and, in particular, quantification of immediate-early gene (IEG) expression, which is a marker of neuronal activation (reviewed in [28]). These studies reveal how impaired extinction is associated with patterns of aberrant neuronal activation in relevant brain circuits.…”

The Effect of Testosterone on the Aldehyde Dehydrogenase Activity in Rats Internal Tissue Under Conditions of Immobilization Stress

“…* p < 0,02 по вiдношенню до групи 3-мiсячних кастрованих тварин; ** p < 0,02 по вiдношенню до групи 3-мiсячних кастрованих та стресованих тварин; 1) p < 0,03 по вiдношенню до групи 2-мiсячних тварин контрольної групи; 2) p < 0,01 по вiдношенню до групи 3-мiсячних тварин контрольної групи; 3) p < 0,03 по вiдношенню до групи 2-мiсячних кастрованих тварин; 4) p < 0,03 по вiдношенню до групи 2-мiсячних кастрованих та стресованих тварин.…”

“…Процеси статевого розвитку ор-ганiзму генетично детермiнованi, але водно-час вони знаходяться пiд впливом ендоген-них та несприятливих факторiв середовища. Зокрема, численнi дослiдження останнiх де-сятилiть дають можливiсть стверджувати, що в перiодi статевого дозрiвання змiню-ється стiйкiсть органiзму до стресу [1][2][3]. Са-ме це може служити однiєю з причин значно-го поширення в пубертатному вiцi серцево-судинних захворювань, неврозiв, патологiї шлунково-кишкового тракту [4,5].…”