Received View of Addiction, Relapse and Treatment

Ndasauka, Yamikani; Wei, Zhengde; Zhang, Xiaochu

doi:10.1007/978-981-10-5562-1_1

Cited by 11 publications

(8 citation statements)

References 52 publications

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“…Substance use disorder causes enormous emotional, economic, medical, and legal costs to individuals and society and a global public health concern with high morbidity and mortality ( 2 ). Current treatments for substance use disorder including pharmacological and/or psychological interventions are available ( 3 ), but the relapse rates are still extremely high up to 50–70% ( 4 ). Additional approaches are needed to reduce relapse rate and strengthen efficacy of current strategies.…”

Section: Introductionmentioning

confidence: 99%

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

et al. 2020

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Deep brain stimulation (DBS) modulates the neuronal activity in specific brain circuits and has been recently considered as a promising intervention for refractory addiction. The insula cortex is the hub of interoception and is known to be involved in different aspects of substance use disorder. In the present study, we investigate the effects of continuous high frequency DBS in the anterior insula (AI) on drug-seeking behaviors and examined the molecular mechanisms of DBS action in morphine-addicted rats. Sprague-Dawley rats were trained to the morphine-conditioned place preference (CPP, day 1–8) followed by bilaterally implanted with DBS electrodes in the AI (Day 10) and recovery (Day 10–15). Continuous high-frequency (HF) -DBS (130 Hz, 150 μA, 90 μs) was applied during withdrawal (Day 16–30) or extinction sessions. CPP tests were conducted on days 16, 30, 40 during withdrawal session and several rats were used for proteomic analysis on day 30. Following the complete extinction, morphine-CPP was reinstated by a priming dose of morphine infusion (2 mg/kg). The open field and novel objective recognition tests were also performed to evaluate the DBS side effect on the locomotion and recognition memory. Continuous HF-DBS in the AI attenuated the expression of morphine-CPP post-withdrawal (Day 30), but morphine addictive behavior relapsed 10 days after the cessation of DBS (Day 40). Continuous HF-DBS reduced the period to full extinction of morphine-CPP and blocked morphine priming-induced recurrence of morphine addiction. HF-DBS in the AI had no obvious effect on the locomotor activity and novel objective recognition and did not cause anxiety-like behavior. In addition, our proteomic analysis identified eight morphine-regulated proteins in the AI and their expression levels were reversely changed by HF-DBS. Continuous HF-DBS in the bilateral anterior insula prevents the relapse of morphine place preference after withdrawal, facilitates its extinction, blocks the reinstatement induced by morphine priming and reverses the expression of morphine-regulated proteins. Our findings suggest that manipulation of insular activity by DBS could be a potential intervention to treat substance use disorder, although future research is warranted.

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Section: Introductionmentioning

confidence: 99%

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

et al. 2020

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“…A high relapse rate is one of the greatest challenges in drug abuse therapy, which may be attributed in part to abnormal memory. 35 , 36 We next employed a confined CPP extinction paradigm ( Pattern 1 in Methods) to investigate whether upregulation of HIF-1α by Rox treatment affects drug-related memory extinction and retrieval (Fig. 2a ).…”

Section: Resultsmentioning

confidence: 99%

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

Yan,

Li,

et al. 2023

Sig Transduct Target Ther

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Substance use disorder remains a major challenge, with an enduring need to identify and evaluate new, translational targets for effective treatment. Here, we report the upregulation of Hypoxia-inducible factor-1α (HIF-1α) expression by roxadustat (Rox), a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α, administered either systemically or locally into selected brain regions, suppressed morphine (Mor)-induced conditioned place preference (CPP). A similar effect was observed with methamphetamine (METH). Moreover, Rox also inhibited the expression of both established and reinstated Mor-CPP and promoted the extinction of Mor-CPP. Additionally, the elevation of HIF-1α enhanced hepcidin/ferroportin 1 (FPN1)-mediated iron efflux and resulted in cellular iron deficiency, which led to the functional accumulation of the dopamine transporter (DAT) in plasma membranes due to iron deficiency-impaired ubiquitin degradation. Notably, iron-deficient mice generated via a low iron diet mimicked the effect of Rox on the prevention of Mor- or METH-CPP formation, without affecting other types of memory. These data reveal a novel mechanism for HIF-1α and iron involvement in substance use disorder, which may represent a potential novel therapeutic strategy for the treatment of drug abuse. The findings also repurpose Rox by suggesting a potential new indication for the treatment of substance use disorder.

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“…One of the characteristics of drug addiction is a high rate of relapse, which has been shown to be closely related to the addict's physiology, emotions, and the environmental stressors they face [20]. Female drug addicts are seriously disturbed by negative emotions, especially the prevalence of depression is higher than that of men, which leads to a higher chance of abuse relapse [21].…”

Section: Discussionmentioning

confidence: 99%

Effects of Different Exercise Modalities on Sex Hormones and Anxiety and Depression in Female Drug Addicts

2023

IJBLS

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To explore the effects of different exercise modes on sex hormones and anxiety and depression of female drug addicts. METHODS: A random sampling method was used to include 30 female drug addicts who met the criteria from the Female Compulsory Drug Rehabilitation Center in Nanan District, Chongqing, China, who were randomly divided into a yoga group (n=10), a physical fitness group (n=10), and a control group (n=10), and underwent intervention training for a period of 12 weeks, 3 times per week, 1 h each time. The subjects' serum luteinizing hormone (LH), pituitary prolactin (PRL), and estradiol (E2) levels were quantitatively detected and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) before and after the intervention. RESULTS: Changes in sex hormone levels of female drug addicts showed that serum luteinizing hormone (LH), pituitary prolactin (PRL), and estradiol (E2) levels were reduced compared with those of the control group. 12 weeks of different training interventions were able to regulate sex hormones, and hormone levels of the Yoga group and the Physical Fitness group were all significantly reduced (P<0.01), and the Yoga group was significantly lower than the Physical Fitness group and the control group (P<0.05); and reduced anxiety (HAHA), and reduced anxiety (HAHA). And reduce anxiety (HAHA) and depression (SDS) status.

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Received View of Addiction, Relapse and Treatment

Cited by 11 publications

References 52 publications

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

Effects of Different Exercise Modalities on Sex Hormones and Anxiety and Depression in Female Drug Addicts

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