Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.
ABSTRACT It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.
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ABSTRACT: Research has elucidated causal links between stress exposure and the development of anxiety disorders, but due to the limited use of female or sex-comparative animal models, little is known about the mechanisms underlying sex differences in those disorders. This is despite an overwhelming wealth of evidence from the clinical literature that the prevalence of anxiety disorders is about twice as high in women compared to men, in addition to gender differences in severity and treatment efficacy. We here review human gender differences in generalized anxiety disorder, panic disorder, posttraumatic stress disorder and anxiety-relevant biological functions, discuss the limitations of classic conflict anxiety tests to measure naturally occurring sex differences in anxiety-like behaviors, describe sex-dependent manifestation of anxiety states after gestational, neonatal, or adolescent stressors, and present animal models of chronic anxiety states induced by acute or chronic stressors during adulthood. Potential mechanisms underlying sex differences in stress-related anxiety states include emerging evidence supporting the existence of two anatomically and functionally distinct serotonergic circuits that are related to the modulation of conflict anxiety and panic-like anxiety, respectively. We discuss how these serotonergic circuits may be controlled by reproductive steroid hormone-dependent modulation of crfr1 and crfr2 expression in the midbrain dorsal raphe nucleus and by estrous stage-dependent alterations of γ-aminobutyric acid (GABAergic) neurotransmission in the periaqueductal gray, ultimately leading to sex differences in emotional behavior.Pflügers Archiv - European Journal of Physiology 04/2013; · 4.87 Impact Factor
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ABSTRACT: Adverse early life experiences (aELEs), such as child abuse, neglect, or trauma, increase lifetime vulnerability for mental illness. In this study, aELEs were modeled in c57bl/6 mice using the maternal separation (MS) paradigm, in which pups were separated for 180min/day (MS180), 15min/day (MS15), or left undisturbed (AFR) from postnatal day 2-14. As adults, pups that experienced MS15 or MS180 demonstrated decreases in tryptophan hydroxylase 2 (TPH2) and serotonin transporter mRNA in the dorsal raphe dorsalis and ventralis, and increases in glucocorticoid receptor mRNA in the dentate gyrus of the hippocampus. To investigate factors underlying shared expression between MS conditions, dam on-nest time and DNA methylation at the TPH2 promoter and 5' UTR were assessed. Post-reunion on-nest time increased as a function of separation duration, potentially serving as a mitigating factor underlying similar expression between MS conditions. TPH2 DNA methylation remained unchanged, suggesting changes in TPH2 mRNA are not mediated by changes in DNA methylation of this region. The shared pattern of expression between MS15 and MS180 conditions suggests a species- or strain- specific response to MS unique to c57bl/6 mice.Brain research 03/2013; · 2.46 Impact Factor
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ABSTRACT: In rodents, the disruption of social rearing conditions before normal weaning induces emotional behavioral abnormalities, such as anxiety, motor activity dysregulation, and stress vulnerability. The beneficial effects of exercise after normal weaning on emotional regulation have been well documented. However, effects of exercise before normal weaning on emotion have not been reported. We examined whether voluntary wheel running (R) during social isolation after early weaning (early weaning/isolation; EI) from postnatal day (PD) 14-30 could prevent EI-induced emotional behavioral abnormalities in Sprague-Dawley rats. Compared with control rats reared with their dam and siblings until PD30, rats performed R during EI (EI+R) and EI rats demonstrated greater locomotion and lower grooming activity in the open-field test (OFT) during the juvenile period. Juvenile EI±R rats showed greater learned helplessness (LH) after exposure to inescapable stress (IS; electric foot shock) than IS-exposed control and EI rats. In contrast, EI rats showed increased locomotion in the OFT and LH after exposure to IS compared with control rats during adulthood; this was not observed in EI±R rats. Both EI and EI±R rats exhibited greater rearing activity in the OFT than controls during adulthood. EI did not increase anxiety in the OFT and elevated plus-maze. These results suggested that R during EI until normal weaning prevented some of the EI-induced behavioral abnormalities, including hyperlocomotor activity and greater LH, during adulthood but not in the juvenile period.Behavioural brain research 02/2014; · 3.22 Impact Factor