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

Fan, Zhixin; Chen, Jie; Li, Ling; Wang, Hanzhang; Gong, Xiayu; Xu, Hanfang; Wu, Lili; Yan, Can

doi:10.1016/j.neures.2021.04.007

Cited by 19 publications

(1 citation statement)

References 60 publications

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“…These findings contradict previous studies indicating that EE can reverse some of drug- or alcohol-induced neuroadaptations within the mesocorticolimbic system ( Lynch et al, 2010 ; Solinas et al, 2010 ; Abel et al, 2019 ; Galaj et al, 2020a ). EE can reverse the effects of stress on behavioral responses and associated CRF signaling ( Francis et al, 2002 ; Sztainberg et al, 2010 ; Fan et al, 2021 ). Specifically, EE can decrease anxiety-like behaviors in mice and reverse the upregulation of CRF1 mRNA level in the basolateral amygdala caused by chronic stress ( Sztainberg et al, 2010 ; Hendriksen et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression

Galaj,

Barrera,

Persaud

et al. 2023

International Journal of Neuropsychopharmacology

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Background There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction Methods and Results Here we investigated the role of midbrain CRF 1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions. Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose-dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in-situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and DAT mRNA in VTA neurons were not impacted by heroin. The Western Blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA Conclusions Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure.

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