Addiction Biology最新文献

{"title":"Involvement of nucleus accumbens SERCA2b in methamphetamine-induced conditioned place preference","authors":"Yujing Wang,&nbsp;Fan Duan,&nbsp;Junda Li,&nbsp;Xiangyu Li,&nbsp;Lingling Xia,&nbsp;Wei Zhao,&nbsp;Ze Wang,&nbsp;Xun Song,&nbsp;Juan Chen,&nbsp;Jingjing Wang,&nbsp;Yue Wang,&nbsp;Jing Zhang,&nbsp;Xiaochu Zhang,&nbsp;Dongliang Jiao","doi":"10.1111/adb.13382","DOIUrl":"10.1111/adb.13382","url":null,"abstract":"<p>Methamphetamine (METH) is a highly addictive psycho-stimulant that induces addictive behaviour by stimulating increased dopamine release in the nucleus accumbens (NAc). The sarco/endoplasmic reticulum calcium ion transport ATPases (SERCA or ATP2A) is a calcium ion (Ca2+) pump in the endoplasmic reticulum (ER) membrane. SERCA2b is a SERCA subtype mainly distributed in the central nervous system. This study used conditioned place preference (CPP), a translational drug reward model, to observe the effects of SERCA and SERCA2b on METH-CPP in mice. Result suggested that the activity of SERCA was significantly decreased in NAc after METH-CPP. Intraperitoneal SERCA agonist CDN1163 injection or bilateral CDN1163 microinjection in the NAc inhibited METH-CPP formation. SERCA2b overexpression by the Adeno-associated virus can reduce the DA release of NAc and inhibit METH-CPP formation. Although microinjection of SERCA inhibitor thapsigargin in the bilateral NAc did not significantly aggravate METH-CPP, interference with SERCA2b expression in NAc by adeno-associated virus increased DA release and promoted METH-CPP formation. METH reduced the SERCA ability to transport Ca2+ into the ER in SHSY5Y cells in vitro, which was reversed by CDN1163. This study revealed that METH dysregulates intracellular calcium balance by downregulating SERCA2b function, increasing DA release in NAc and inducing METH-CPP formation. Drugs that target SERCA2b may have the potential to treat METH addiction.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paternal preconception alcohol consumption increased Angiotensin II-mediated vasoconstriction in male offspring cerebral arteries via oxidative stress-AT1R pathway","authors":"Ze Zhang,&nbsp;Yumeng Zhang,&nbsp;Mingxing Liu,&nbsp;Hongyu Su,&nbsp;Yun He,&nbsp;Qiutong Zheng,&nbsp;Zhice Xu,&nbsp;Jiaqi Tang","doi":"10.1111/adb.13385","DOIUrl":"10.1111/adb.13385","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca²⁺) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BK_C_a) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca²⁺ channel and endoplasmic reticulum and decreased BK_Ca function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of interventions on smoking cessation: A systematic review and network meta-analysis","authors":"Ying Li,&nbsp;Lei Gao,&nbsp;Yaqing Chao,&nbsp;Jianhua Wang,&nbsp;Tianci Qin,&nbsp;Xiaohua Zhou,&nbsp;Xiaoan Chen,&nbsp;Lingyu Hou,&nbsp;linlin Lu","doi":"10.1111/adb.13376","DOIUrl":"10.1111/adb.13376","url":null,"abstract":"<p>A network meta-analysis (NMA) including randomized controlled trials (RCTs) was conducted to evaluate the effects of different interventions on smoking cessation. Studies were collected from online databases including PubMed, EMBASE, Cochrane Library, and Web of Science based on inclusion and exclusion criteria. Eligible studies were further examined in the NMA to compare the effect of 14 interventions on smoking cessation. Thirty-four studies were examined in the NMA, including a total of 14 interventions and 28 733 participants. The results showed that health education (HE; odds ratio ([OR] = 200.29, 95% CI [1.62, 24 794.61])), other interventions (OI; OR = 29.79, 95% CI [1.07, 882.17]) and multimodal interventions (MUIs; OR = 100.16, 95% CI [2.06, 4867.24]) were better than self-help material (SHM). HE (OR = 243.31, 95% CI [1.39, 42531.33]), MUI (OR = 121.67, 95% CI [1.64, 9004.86]) and financial incentive (FI; OR = 14.09, 95% CI [1.21, 164.31]) had positive effects on smoking cessation rate than smoking cessation or quitting APP (QA). Ranking results showed that HE (83.6%) and motivation interviewing (MI; 69.6%) had better short-term effects on smoking cessation. HE and MUI provided more smoking cessation benefits than SHM and QA. FI was more effective at quitting smoking than QA. Also, HE and MI were more likely to be optimal smoking cessation interventions.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical and subcortical microstructure integrity changes after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and relates to clinical outcomes","authors":"Jalil Rasgado-Toledo,&nbsp;Victor Issa-Garcia,&nbsp;Ruth Alcalá-Lozano,&nbsp;Eduardo A. Garza-Villarreal,&nbsp;Gabriel González-Escamilla","doi":"10.1111/adb.13381","DOIUrl":"10.1111/adb.13381","url":null,"abstract":"<p>Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [<i>n</i> = 23] and active [<i>n</i> = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Isopropylbenzylamine-induced conditioned place preference, sensitization behaviour and self-administration in rodents","authors":"Miaojun Lai,&nbsp;Dan Fu,&nbsp;Xiangyu Li,&nbsp;Dingding Zhuang,&nbsp;Majie Wang,&nbsp;Zeming Xu,&nbsp;Huifen Liu,&nbsp;Haowei Shen,&nbsp;Peng Xu,&nbsp;Wenhua Zhou","doi":"10.1111/adb.13370","DOIUrl":"10.1111/adb.13370","url":null,"abstract":"<p><i>N</i>-Isopropylbenzylamine (<i>N</i>-ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of <i>N</i>-ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of <i>N</i>-ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self-administration tests. The results showed that <i>N</i>-ipb at a dose of 3 mg·kg⁻¹ significantly induced CPP in mice, which was comparable to the effect of METH at 1 mg·kg⁻¹. Either acute or repeated <i>N</i>-ipb injections (1 or 3 mg·kg⁻¹) failed to raise the locomotor activity. However, acute treatment with 10 mg·kg⁻¹ <i>N</i>-ipb elevated the locomotor activity compared with saline, while chronic injection of 10 mg·kg⁻¹ <i>N</i>-ipb induced a delayed and attenuated sensitization compared with 1 mg·kg⁻¹ METH. Rats could acquire <i>N</i>-ipb self-administration at a dose of 1 mg·kg⁻¹·infusion⁻¹, and a typical inverted U-shaped dose–response curve was obtained for <i>N</i>-ipb. The mean dose of <i>N</i>-ipb that maintained the maximum response was greater than that of METH, indicating that <i>N</i>-ipb is less potent for reinforcement than METH. In the economic behavioural analysis, comparison of essential values derived from the demand elasticity revealed that <i>N</i>-ipb is less efficacy as a reinforcer than METH. The present data demonstrate that <i>N</i>-ipb functions as a reinforcer and has a potential for abuse. However, the potency of psychomotor stimulation and the reinforcing effectiveness of <i>N</i>-ipb are lower than those of METH.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural response to threat and reward among young adults at risk for alcohol use disorder","authors":"Katelyn T. Kirk-Provencher,&nbsp;Rosa H. Hakimi,&nbsp;Keinada Andereas,&nbsp;Anne E. Penner,&nbsp;Joshua L. Gowin","doi":"10.1111/adb.13378","DOIUrl":"10.1111/adb.13378","url":null,"abstract":"<p>Alcohol use disorder (AUD) is heritable. Thus, young adults with positive family histories represent an at-risk group relative to those without a family history, and if studied at a time when both groups have similar levels of alcohol use, it provides an opportunity to identify neural processing patterns associated with risk for AUD. Previous studies have shown that diminished response to potential reward is associated with genetic risk for AUD, but it is unclear how threat may modulate this response. We used a modified Monetary Incentive Delay task during fMRI to examine neural correlates of the interaction between threat and reward anticipation in a sample of young adults with (<i>n</i> = 31) and without (<i>n</i> = 44) family histories of harmful alcohol use. We found an interaction (<i>p</i> = 0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history-positive group also reported less excitement for trials to gain $5 relative to gaining $0 (<i>p</i> &lt; 0.001). Family history-positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history-negative individuals (<i>p</i> = 0.005), but the groups did not differ as a function of threat (<i>p</i> &gt; 0.70). Young adults with, relative to without, enriched risk for AUD may have diminished reward processing via both neural and behavioural markers to potential rewarding and negative consequences. Neural response to threat may not be a contributing factor to risk at this stage.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphine exposure modulates dimensional bias and set formation in anthropoids","authors":"Sadegh Ghasemian,&nbsp;Alexander J. Pascoe,&nbsp;Marzieh M. Vardanjani,&nbsp;Zakia Z. Haque,&nbsp;Anna Ignatavicius,&nbsp;Daniel J. Fehring,&nbsp;Vahid Sheibani,&nbsp;Farshad A. Mansouri","doi":"10.1111/adb.13380","DOIUrl":"10.1111/adb.13380","url":null,"abstract":"<p>Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension-related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target-defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event-related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant ‘switch cost’. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine-induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long-lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia activity in the human basal ganglia is altered in alcohol use disorder and reversed with remission from alcohol","authors":"Ameer Elena Rasool,&nbsp;Teri Furlong,&nbsp;Asheeta A. Prasad","doi":"10.1111/adb.13374","DOIUrl":"https://doi.org/10.1111/adb.13374","url":null,"abstract":"<p>Alcohol use disorder (AUD) is characterized by cycles of abuse, withdrawal, and relapse. Neuroadaptations in the basal ganglia are observed in AUD; specifically in the putamen, globus pallidus (GP), and ventral pallidum (VP). These regions are associated with habit formation, drug-seeking behaviors, and reward processing. While previous studies have shown the crucial role of glial cells in drug seeking, it remains unknown whether glial cells in the basal ganglia are altered in AUD. Glial cells in the putamen, GP, and VP were examined in human post-mortem tissue of AUD and alcohol remission cases. Immunohistochemistry was performed to analyze cell count, staining intensity, and morphology of microglia and astrocytes, using markers Iba-1 and GFAP. Morphological analysis revealed a significant decrease in microglia cell size and process retraction, indicating activation or a dystrophic microglia phenotype in individuals with AUD compared to controls. Microglia staining intensity was also higher in the GP and VP in AUD cases, whereas microglia staining intensity and cell size in remission cases were not different to control cases. In contrast, no astrocyte changes were observed in examined brain regions for both AUD and remission cases compared to controls. These results suggest alcohol exposure alters microglia, potentially contributing to dysfunctions in the basal ganglia that maintain addiction, and abstinence from alcohol may reverse microglia changes and associated dysfunctions. Overall, this study further characterizes AUD neuropathology and implicates microglia in the putamen, GP, and VP as a potential target for therapy.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of online poker gambling on behavioural and neurophysiological responses to a virtual gambling task","authors":"Julie Giustiniani,&nbsp;Magali Nicolier,&nbsp;Audrey Diwoux,&nbsp;Thibaut Chabin,&nbsp;Lionel Pazart,&nbsp;Emmanuel Haffen,&nbsp;Damien Gabriel","doi":"10.1111/adb.13373","DOIUrl":"https://doi.org/10.1111/adb.13373","url":null,"abstract":"<p>Online poker gambling (OPG) involves various executive control processes and emotion regulation. In this context, we hypothesized that online poker players, accustomed to handling virtual cards, would show high performance on computerized decision-making tasks such as the Iowa Gambling Task (IGT). Using press advertisements, we recruited a non-gambler group (NG; <i>n</i> = 20) and an OPG group (<i>n</i> = 22). All participants performed the IGT while their cerebral activity was recorded by electroencephalography. Compared with the OPG group, the NG group showed significantly better progression in the IGT in the last trials. Recording of brain activity revealed the appearance of a temporal map between 150 and 175 ms specific to the gain condition in both groups. A second map was observed at 215–295 ms specifically in the NG group, and the generators were identified in the occipital regions. This activity is indicative of a high level of visual awareness; thus, it reflects additional processing of visual information, which <i>can be assumed to</i> be induced by the lower exposure of the NGs to online card games. We hypothesize that the absence of this activity in the OPG group might be due to their online habituation to virtual environments.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential cannabinoid-like effects and pharmacokinetics of ADB-BICA, ADB-BINACA, ADB-4en-PINACA and MDMB-4en-PINACA in mice: A comparative study","authors":"Fenghua Zhou,&nbsp;Xiaoli Wang,&nbsp;Sujun Tan,&nbsp;Yan Shi,&nbsp;Bing Xie,&nbsp;Ping Xiang,&nbsp;Bin Cong,&nbsp;Chunling Ma,&nbsp;Di Wen","doi":"10.1111/adb.13372","DOIUrl":"https://doi.org/10.1111/adb.13372","url":null,"abstract":"<p>Despite synthetic cannabinoids' (SCs) prevalent use among humans, these substances often lack comprehensive pharmacological data, primarily due to their rapid emergence in the market. This study aimed to discern differences and causal factors among four SCs (ADB-BICA, ADB-BINACA, ADB-4en-PINACA and MDMB-4en-PINACA), with respect to locomotor activity, body temperature and nociception threshold. Adult male C57BL/6 mice received intraperitoneal injections of varying doses (0.5, 0.1 and 0.02 mg/kg) of these compounds. Three substances (including ADB-BINACA, ADB-4en-PINACA and MDMB-4en-PINACA) demonstrated dose- and time-dependent hypolocomotive and hypothermic effects. Notably, 0.1 mg/kg MDMB-4en-PINACA exhibited analgesic properties. However, ADB-BICA did not cause any effects. MDMB-4en-PINACA manifested the most potent and sustained effects, followed by ADB-4en-PINACA, ADB-BINACA and ADB-BICA. Additionally, the cannabinoid receptor 1 (CB1R) antagonist AM251 suppressed the effects induced by acute administration of the substances. Analysis of molecular binding configurations revealed that the four SCs adopted a congruent C-shaped geometry, with shared linker binding pockets conducive to robust steric interaction with CB1R. Essential residues PHE²⁶⁸, PHE²⁰⁰ and SER¹⁷³ within CB1R were identified as pivotal contributors to enhancing receptor–ligand associations. During LC-MS/MS analysis, 0.5 mg/kg MDMB-4en-PINACA exhibited the highest plasma concentration and most prolonged detection window post-administration. The study of SCs' pharmacological and pharmacokinetic profiles is crucial for better understanding the main mechanisms of cannabinoid-like effects induced by SCs, interpreting clinical findings related to SC uses and enhancing SCs risk awareness.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139700649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}