Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal

Li, Yixin; Xia, Baijuan; Li, Rongrong; Dai, Yu‐Tzu; Wang, Yanlin; Wenmei, Liang

doi:10.1097/wnr.0000000000000810

Cited by 19 publications

(5 citation statements)

References 35 publications

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“…In our study, the weight of rats in the HA and HR groups was lower than that of rats in the control group. These results are in agreement with previous observation (Li, Xia, Li, Yin, Wang, et al 2017) and were probably caused by heroin-mediated activation of mu-opioid receptors in the intestinal wall and inhibition of pathways in the enteric nervous system, resulting in reduced peristalsis and slowed intestinal transit (Leppert 2015). Moreover, the weight loss of rats in the HR group was more pronounced, which may have been because long-term continuous addiction leads to more serious gastrointestinal damage.…”

Section: Behavior and Weight Losssupporting

confidence: 92%

Detection of heroin addiction- and relapse-induced axonal transport dysfunction in the brain in vivo by MRI

Yang

Luo

Liao

et al. 2022

Preprint

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Purpose Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport in different stages after heroin addiction.Methods Rodent models of heroin addiction (HA) and heroin relapse (HR) were established by injection of different doses of heroin solution at different times. Heroin-induced learning and memory deficits were evaluated by the Morris water maze (MWM). MEMRI was used to dynamically evaluate axonal transport through the olfactory pathway. The expression of proteins related to axonal structure and function were assessed by western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes. Neurofilament heavy chain (NF-H) protein levels were analyzed by immunofluorescence staining.Result HA model rats and especially HR model rats showed worse spatial learning and memory abilities than control rats. Compared with HA model rats and control rats, HR model rats exhibited a significant increase in escape latency and significant decreases in the number of platform location crossings and time spent in the target quadrant. Mn2+ transport was accelerated in HA model rats. HR model rats exhibited a severely insufficient capacity for Mn2+ transport, and the axonal transport rate (ATR) was significantly reduced in these rats compared to control rats (P<0.001). The levels of cytoplasmic dynein and KIF5 in rats in the HR group were significantly decreased (P<0.001), and the levels of energy-related proteins, including COX IV and ATPB, were lower in the HR group than the control group (P<0.001). The brains of heroin-exposed rats showed an abnormal ultrastructure, exhibiting neuronal apoptosis and mitochondrial dysfunction. Heroin decreased the expression of NF-H, with the staining intensity being significantly reduced in tissues from HA and HR model rats (P<0.05).Conclusion MEMRI can detect axonal transport dysfunction caused by long-term repeated exposure to heroin, and decreases in the levels of motor proteins and mitochondrial dysfunction may be the main causes of this axonal transport impairment. Thus, the study shows that MEMRI is a potential tool for visualizing axonal transport in individuals experiencing drug addiction, providing a new direction for the evaluation of addictive drug withdrawal.

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Section: Behavior and Weight Losssupporting

confidence: 92%

Detection of heroin addiction- and relapse-induced axonal transport dysfunction in the brain in vivo by MRI

Yang

Luo

Liao

et al. 2022

Preprint

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“… 30 The expression levels of BDNF in the NAc of rats significantly decrease after chronic heroin treatment, whereas BDNF expression is significantly increased in these rats when they undergo either naloxone‐induced withdrawal or spontaneous withdrawal 1 day after the last heroin treatment. 31 However, this explanation is in conflict with that of another study that suggests that BDNF protein in the NAc is not involved in heroin incubation. 21 Several methodological issues should be considered when these discrepant results are interpreted.…”

Section: Discussionmentioning

confidence: 88%

Akt and its phosphorylation in nucleus accumbens mediate heroin‐seeking behavior induced by cues in rats

et al. 2021

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Akt is initially identified as one of the downstream targets of phosphatidylinositol‐3 kinase (PI3K) and is involved in morphine reward and tolerance. However, whether phospholyration of Akt (p‐Akt) mediates heroin relapse remains unclear. Here, we aimed to explore the role of p‐Akt in the nucleus accumbens (NAc) in cue‐induced heroin‐seeking behaviors after withdrawal. First, rats were trained to self‐administer heroin for 14 days, after which we assessed heroin‐seeking behaviors induced by a context cue (CC) or by discrete conditioned cues (CS) after 1 day or 14 days of withdrawal. We found that the active responses induced by CC or CS after 14 days of withdrawal were higher than those after 1 day of withdrawal. Meanwhile, the expression of p‐Akt in the NAc was also greatest when rats were exposed to the CS after 14 days of withdrawal. Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS‐induced heroin‐seeking behaviors after 14 days of withdrawal, paralleling the decreased levels of p‐Akt in the NAc. Finally, Akt1 or β‐arrestin 2 was downregulated via a lentiviral injection to assess the effect on heroin seeking after 14 days of withdrawal. CS‐induced heroin‐seeking behavior was inhibited by downregulation of Akt1, but not β‐arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin‐seeking behavior, suggesting that the PI3K/Akt pathways may be involved in the process of heroin relapse and addiction.

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“…To further explore the underlying mechanism, the community succession of the gut microbiome was detected after various treatments via 16S rRNA sequencing. The findings revealed that His treatment increased the relative abundance of Proteobacteria, indicating the occurrence of dysbiosis (Li et al, 2017). At the genus level, His treatment promoted Lachnospirace-ae_NK4A136_group and norank_f_Lachnospiracae relative abundance, which was reported to be increased by Fubrick tea attenuates (Shin et al, 2015).…”

Section: Discussionmentioning

confidence: 86%

Histamine-regulated brain-derived neurotrophic factor (BDNF) catabolism by specific gut microbiota in mice

Luo,

Shi,

Liu

et al. 2023

IFRJ

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Huangjiu usually causes excessive intoxication. Although the primary components, including β-benzyl ethanol, isopentanol, histamine, and phenethylamine are linked to intoxication, the underlying mechanism remains obscure. The present work thus analysed the effects of oral treatment of these components, particularly histamine, and discovered which of these components induced oxidative stress and inflammatory cytokine responses in mice serum and cerebrum. Lipopolysaccharide levels were elevated, and the gut microbiota was recomposed. Additionally, the catabolic pathway of the brain-derived neurotrophic factor was investigated. The correlation analysis revealed a possible correlation between gut microbiota changes and neurotransmitter imbalance. Based on the findings, histamine might alter the gut microbiota composition, affect the inflammatory LPS accumulation, and modulate the gut-brain axis, thus leading to an increase in oxidative stress, inflammatory response, and neurotransmitter imbalance in the brain. The present work provided a baseline for future research into the effects of Huangjiu, and enhanced our understanding of treating and preventing associated inflammatory diseases.

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Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal

Cited by 19 publications

References 35 publications

Detection of heroin addiction- and relapse-induced axonal transport dysfunction in the brain in vivo by MRI

Detection of heroin addiction- and relapse-induced axonal transport dysfunction in the brain in vivo by MRI

Akt and its phosphorylation in nucleus accumbens mediate heroin‐seeking behavior induced by cues in rats

Histamine-regulated brain-derived neurotrophic factor (BDNF) catabolism by specific gut microbiota in mice

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