Pairing of neonatal phencyclidine exposure and acute adolescent stress in male rats as a novel developmental model of schizophrenia

Abstract: Background: Stress during adolescence is usually associated with psychopathology later in life. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience. Methods: Sprague Dawley rats (50 males, 48 females) were subjected to adolescent chronic variable stress (adol CVS) for 2-weeks at PND45. At PND 85, a group was subjected to single prolonged stress (SPS). After a week, animals were evaluated in an auditory-cued fear conditioning paradigm and neuronal recruitment during reinstatement was assessed by Fos expression. Patch clamp electrophysiology (17-35 cells/group) was performed in male rats to examine physiological changes associated with resilience. Results: Adol CVS blocked fear potentiation evoked by SPS. We observed that SPS impaired extinction (males) and enhanced reinstatement (both sexes) of the conditioned freezing response. Prior adol CVS prevented both effects. SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both also prevented by adol CVS, suggesting different neurocircuits involved in generating resilience between sexes. We explored the mechanism behind reduced IL recruitment by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons and prior adol CVS prevented this effect. Conclusion: Our data indicate that adolescent stress can impart resilience to the effects of traumatic stress on neuroplasticity and behavior. Our data provide a mechanistic link behind developmental stress induced behavioral resilience and prefrontal (IL) cortical excitability.

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Adolescent Stress Increases Adult Ethanol Self-administration and Alters Ventral Tegmental Area GABA Signaling

10.1101/715607 ◽

2019 ◽

Author(s):

David A Connor ◽

Ruthie E Wittenberg ◽

Jillian Drogin ◽

Allison Mak ◽

John A Dani

Keyword(s):

Life Stress ◽

Early Life ◽

Alcohol Use Disorders ◽

Early Life Stress ◽

Male Rats ◽

Stress Exposure ◽

Self Administration ◽

Adolescent Stress ◽

Gaba Signaling

AbstractAlcohol use disorders (AUDs) continue to be a significant public health problem. Early life stress and adversity have long-lasting effects on a wide range of behaviors, including responses to drugs of abuse. Epidemiological evidence indicates that exposure to early life stress contributes to alcohol use disorders and, while it is known that stress and alcohol both act on overlapping mesolimbic circuitry, the cellular mechanisms underlying the relationship between stress and alcohol intake are not well understood. Previous work has demonstrated that acute stress increases ethanol intake mediated by changes in GABA signaling within the ventral tegmental area (VTA). Here we investigated if adolescent stress exposure might elicit long-term, persistent increases in ethanol self-administration associated with altered VTA GABA signaling. To this end, we exposed adolescent postnatal day (PND) 28 male rats to 14 days of chronic variable stress (CVS) and then examined operant ethanol self-administration begun at least 30 days later. We found that adolescent stress exposure resulted in significantly increased ethanol self-administration in adulthood. In contrast, adult (PND 82) male rats exposed to the same CVS protocol did not display increased ethanol self-administration that was begun 30 days later. Furthermore, we found that adolescent stress exposure resulted in enhancement of ethanol-induced GABA signaling onto VTA dopamine neurons and impairments in VTA GABA chloride homeostasis. The results indicate that adolescence is a period vulnerable to stress, which produces long-term changes in VTA GABA signaling associated with increased ethanol self-administration behavior.

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Early adolescent stress-induced changes in prefrontal cortex miRNA-135a and hippocampal miRNA-16 in male rats

Developmental Psychobiology ◽

10.1002/dev.21558 ◽

2017 ◽

Vol 59 (8) ◽

pp. 958-969 ◽

Cited By ~ 8

Author(s):

Yuan Liu ◽

Dexiang Liu ◽

Jingjing Xu ◽

Hong Jiang ◽

Fang Pan

Keyword(s):

Prefrontal Cortex ◽

Male Rats ◽

Early Adolescent ◽

Adolescent Stress ◽

Induced Changes

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Environmental enrichment modulates HPA axis reprogramming in adult male rats exposed to early adolescent stress

Neuroscience Research ◽

10.1016/j.neures.2021.04.007 ◽

2021 ◽

Author(s):

Zhixin Fan ◽

Jie Chen ◽

Ling Li ◽

Hanzhang Wang ◽

Xiayu Gong ◽

...

Keyword(s):

Hpa Axis ◽

Adult Male ◽

Environmental Enrichment ◽

Male Rats ◽

Early Adolescent ◽

Adolescent Stress

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Beneficial Effects of Physical Activity and Crocin Against Adolescent Stress Induced Anxiety or Depressive-Like Symptoms and Dendritic Morphology Remodeling in Prefrontal Cortex in Adult Male Rats

Neurochemical Research ◽

10.1007/s11064-019-02727-2 ◽

2019 ◽

Vol 44 (4) ◽

pp. 917-929 ◽

Cited By ~ 7

Author(s):

Mohadeseh Ghalandari-Shamami ◽

Shahla Nourizade ◽

Behpour Yousefi ◽

Abbas Ali Vafaei ◽

Roghayeh Pakdel ◽

...

Keyword(s):

Physical Activity ◽

Prefrontal Cortex ◽

Adult Male ◽

Dendritic Morphology ◽

Male Rats ◽

Beneficial Effects ◽

Adolescent Stress

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Repeated stress exposure in mid-adolescence attenuates behavioral, noradrenergic, and epigenetic effects of trauma-like stress in early adult male rats

Scientific Reports ◽

10.1038/s41598-020-74481-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lauren E. Chaby ◽

Nareen Sadik ◽

Nicole A. Burson ◽

Scott Lloyd ◽

Kelly O’Donnel ◽

...

Keyword(s):

Histone Deacetylases ◽

Brain Regions ◽

Male Rats ◽

Cognitive Effects ◽

Severe Stress ◽

Stress History ◽

Stress Regulation ◽

Adolescent Stress ◽

Epigenetic Effects ◽

Prolonged Stress

Abstract Stress in adolescence can regulate vulnerability to traumatic stress in adulthood through region-specific epigenetic activity and catecholamine levels. We hypothesized that stress in adolescence would increase adult trauma vulnerability by impairing extinction-retention, a deficit in PTSD, by (1) altering class IIa histone deacetylases (HDACs), which integrate effects of stress on gene expression, and (2) enhancing norepinephrine in brain regions regulating cognitive effects of trauma. We investigated the effects of adolescent-stress on adult vulnerability to severe stress using the single-prolonged stress (SPS) model in male rats. Rats were exposed to either (1) adolescent-stress (33–35 postnatal days) then SPS (58–60 postnatal days; n = 14), or (2) no adolescent-stress and SPS (58–60 postnatal days; n = 14), or (3) unstressed conditions (n = 8). We then measured extinction-retention, norepinephrine, HDAC4, and HDAC5. As expected, SPS exposure induced an extinction–retention deficit. Adolescent-stress prior to SPS eliminated this deficit, suggesting adolescent-stress conferred resiliency to adult severe stress. Adolescent-stress also conferred region-specific resilience to norepinephrine changes. HDAC4 and HDAC5 were down-regulated following SPS, and these changes were also modulated by adolescent-stress. Regulation of HDAC levels was consistent with the pattern of cognitive effects of SPS; only animals exposed to SPS without adolescent-stress exhibited reduced HDAC4 and HDAC5 in the prelimbic cortex, hippocampus, and striatum. Thus, HDAC regulation caused by severe stress in adulthood interacts with stress history such that seemingly conflicting reports describing effects of adolescent stress on adult PTSD vulnerability may stem in part from dynamic HDAC changes following trauma that are shaped by adolescent stress history.

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