Psychopharmacology最新文献

{"title":"The impact of voluntary wheel-running exercise on hippocampal neurogenesis and behaviours in response to nicotine cessation in rats.","authors":"Magdalena Zaniewska, Sabina Brygider, Iwona Majcher-Maślanka, Dawid Gawliński, Urszula Głowacka, Sława Glińska, Łucja Balcerzak","doi":"10.1007/s00213-024-06705-7","DOIUrl":"10.1007/s00213-024-06705-7","url":null,"abstract":"<p><strong>Rationale: </strong>The literature indicates that nicotine exposure or its discontinuation impair adult hippocampal neurogenesis in rats, though the impact of exercise on this process remains unclear. We have previously shown that disturbances in the number of doublecortin (DCX, a marker of immature neurons)-positive (DCX⁺) cells in the dentate gyrus (DG) of the hippocampus during nicotine deprivation may contribute to a depression-like state in rats.</p><p><strong>Objectives: </strong>This study aimed to investigate the effect of running on hippocampal neurogenesis, depression-like symptoms, and drug-seeking behaviour during nicotine deprivation.</p><p><strong>Methods: </strong>The rats were subjected to nicotine (0.03 mg/kg/inf) self-administration via an increasing schedule of reinforcement. After 21 sessions, the animals entered a 14-day abstinence phase during which they were housed in either standard home cages without wheels, cages equipped with running wheels, or cages with locked wheels.</p><p><strong>Results: </strong>Wheel running increased the number of K_i-67⁺ and DCX⁺ cells in the DG of both nicotine-deprived and nicotine-naive rats. Wheel-running exercise evoked an antidepressant effect on abstinence Day 14 but had no effect on nicotine-seeking behaviour on abstinence Day 15 compared to rats with locked-wheel access.</p><p><strong>Conclusions: </strong>In summary, long-term wheel running positively affected the number of immature neurons in the hippocampus, which corresponded with an antidepressant response in nicotine-weaned rats. One possible mechanism underlying the positive effect of running on the affective state during nicotine cessation may be the reduction in deficits in DCX⁺ cells in the hippocampus.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2585-2607"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506715","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":"Evaluation of (S)-T1 and (S)-T2 ligands targeting α3β4 nAChR as potential nicotine addiction pharmacotherapy.","authors":"Saranda Nianpanich, Ratchanee Rodsiri, Ridho Islamie, Patanachai Limpikirati, Thanundorn Thanusuwannasak, Opa Vajragupta, Apinan Kanasuwan, Jiradanai Sarasamkan","doi":"10.1007/s00213-024-06675-w","DOIUrl":"10.1007/s00213-024-06675-w","url":null,"abstract":"<p><strong>Objectives: </strong>Substance use disorders (SUDs) represent a significant global health concern, demanding the development of effective pharmacological treatments. To address this, an investigation was conducted to examine the anti-addictive properties of two compounds, (S)-T1 and (S)-T2, which specifically target the α3β4 nicotinic acetylcholine receptor (nAChR).</p><p><strong>Methods: </strong>The effects of (S)-T1 and (S)-T2 on nicotine-induced conditioned place preference (CPP), locomotor activity and dopamine levels in particular brain regions associated to addiction were investigated and compared in male C57BL/6N mice.</p><p><strong>Results: </strong>The results demonstrate that neither (S)-T1 nor (S)-T2 induced place conditioning or conditioned place aversion (CPA), suggesting the absence of rewarding or aversive effects. Both compounds significantly attenuated nicotine-induced CPP, with (S)-T1 exhibiting a dose-dependent effect. Furthermore, the co-administration of (S)-T2 (10 mg/kg) with nicotine markedly reduced locomotor activity compared to nicotine treatment alone. Additionally, dopamine analysis revealed that nicotine increased dopamine levels in the nucleus accumbens (NAc) and dorsal striatum, whereas the co-administration of (S)-T1 (1, 3, and 10 mg/kg) and (S)-T2 (10 mg/kg) significantly decreased dopamine levels in these brain regions. No significant effects were observed in the prefrontal cortex (PFC).</p><p><strong>Conclusions: </strong>These findings suggest that (S)-T1 and (S)-T2 hold promise for treating nicotine addiction by attenuating nicotine-induced CPP and modulating dopamine release in key reward-related brain regions. Further research is needed to gain insights into the underlying mechanisms behind their anti-addictive effects and substantiate their potential for treating nicotine addiction.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2485-2495"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036769","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":"Bioinformatics analysis of the mechanisms of traumatic brain injury-associated dementia based on the competing endogenous RNA.","authors":"Changmeng Cui, Li Zhu, Guangkui Han, Jianping Sun, Liang Zhang, Yujin Guo, Pei Jiang","doi":"10.1007/s00213-024-06691-w","DOIUrl":"10.1007/s00213-024-06691-w","url":null,"abstract":"<p><strong>Rationale: </strong>Traumatic brain injury (TBI) is a critical condition associated with cognitive impairments, including dementia. This study is aimed to construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network based on bioinformatics analysis and explore molecular mechanisms underlying post-TBI dementia.</p><p><strong>Methods: </strong>GSE104687 and GSE205661 datasets were downloaded from Gene Expression Omnibus database. Molecular Signatures Database (MSigDB) was used to search oxidative stress-, metabolism- and immune-related genes as the target gene datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were carried out for functional annotation and enrichment analysis. A TBI mouse model was built to validate the expression of NF2, PLXNA2, NCBP2 and U2SURP in brain tissues.</p><p><strong>Results: </strong>A total of 7 differentially expressed lncRNAs (DElncRNAs) and 191 DEmRNAs were obtained. Subsequent to differential expression (DE) analysis, a lncRNA-miRNA-mRNA network was established. Notably, 13 key DEmRNAs were identified, potentially playing pivotal roles in the pathogenesis of TBI-induced dementia. By comparing the target gene datasets with 13 DEmRNAs, we identified 4 target genes that overlap with the 13 DEGmRNAs, namely NF2, PLXNA2, NCBP2 and U2SURP. Functional enrichment analysis highlighted the involvement of neuronal projections in the dementia-enriched cluster, while the protective cluster showed associations with protein synthesis and ubiquitination pathways. Importantly, we explored potential drug interventions based on interactions with the above 4 target genes. Additionally, drug interaction prediction showed that NF2 could interact with SELUMETINIB, EVEROLIMUS and TEMSIROLIMUS.</p><p><strong>Conclusion: </strong>Our study provides insights into the complex regulatory networks underlying post-TBI dementia and suggests a potential role for three classes of drugs in managing dementia symptoms in TBI-induced dementia.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2441-2452"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352685","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":"Obtusin ameliorates diabetic retinopathy by inhibiting oxidative stress and inflammation.","authors":"Jingyi Xu, Rongjing Shen, Mengting Qian, Luying Ning, Xinyu Zhang, Bingqing Xie, Yong Jiang, Zhengjun Zhou, Wei Dong","doi":"10.1007/s00213-024-06689-4","DOIUrl":"10.1007/s00213-024-06689-4","url":null,"abstract":"<p><strong>Rationale: </strong>Diabetic retinopathy (DR) is linked to an increased risk of psychiatric and neurological conditions, largely due to chronic inflammation, oxidative stress, and microvascular damage associated with the disease. Emerging evidence suggests that Cassia seed extract has significant anti-inflammatory and antioxidant properties. However, the therapeutic potential of obtusin, a major compound in Cassia seed, and its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aimed to evaluate the therapeutic efficacy of obtusin in the treatment of DR.</p><p><strong>Methods: </strong>Db/db mice were treated with obtusin (5 and 10 mg/kg/day) for 12 weeks. Throughout the study, body weight, blood glucose levels, and lipid profiles were monitored. Retinal histopathology and transmission electron microscopy were used to assess the pharmacological effects of obtusin in vivo. Additionally, in vitro assays were conducted on human retinal microvascular endothelial cells cultured under high glucose conditions to explore obtusin's potential role in mitigating DR.</p><p><strong>Results: </strong>Obtusin treatment in diabetic mice significantly reduced blood glucose levels, improved dyslipidemia, thickened retinal layers, reduced retinal oxidative stress, and inhibited the upregulation of inflammatory cytokines. It also lessened fundus microangiopathy and preserved the retina's normal barrier function. Mechanistic in vitro analysis suggested that obtusin targets the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway, both of which are implicated in DR.</p><p><strong>Conclusions: </strong>Our findings suggest that the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway could be therapeutic targets for obtusin in the treatment of DR and its associated psychiatric and neurological conditions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2471-2484"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564847","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":"Characterization of the nicotine uptake and safety of Nordic spirit tobacco-free oral nicotine pouches: A randomized cross-over study.","authors":"Karine Renard, Daisuke Nishihara, Johan Nilsson, Sylvain Larroque, Javier Martinez, Lesley Giles","doi":"10.1007/s00213-024-06721-7","DOIUrl":"https://doi.org/10.1007/s00213-024-06721-7","url":null,"abstract":"<p><strong>Rationale: </strong>Given the nascency of tobacco-free oral nicotine pouches (NPs) and the heterogeneity of commercially available NP brands, there is a need for scientific evaluation of different NP formulations. Nordic Spirit, novel NPs are distinguished by their unique composition.</p><p><strong>Objectives: </strong>To characterize blood nicotine delivery, pharmacokinetics (PK), subjective and physiological effects and to monitor safety of three Nordic Spirit NPs (6 mg, 9 mg and 11.2 mg/pouch) compared with LD tobacco snus (11.2 mg/pouch) and Nicorette® gum (4 mg/unit) following single 30 min use.</p><p><strong>Methods: </strong>This was a randomized, open-label, ten-sequence, single-use, cross-over clinical study with 30 healthy adult Swedish snus users.</p><p><strong>Results: </strong>Peak nicotine concentrations (C_max) ranged from 10.92 to 17.32 ng/mL for the three Nordic Spirit NPs, with a trend toward dose proportionality, and 8.18 ng/mL and 9.23 ng/mL for the LD snus and Nicorette® gum comparators, respectively. Peak concentration for Nordic Spirit NPs was reached (T_max) after 30 to 38 min, and after 45 min for LD snus and Nicorette® gum. No notable safety concerns were observed after single use for any of the study products.</p><p><strong>Conclusions: </strong>Delivery of nicotine from the three Nordic Spirit NPs appeared to be nicotine content-dependent, based on C_max and AUC. The amount of nicotine extracted showed positive correlation with the reported C_max and AUC. For Nordic Spirit NPs, T_max was immediately after end of use. The characteristics of Nordic Spirit NPs were found to be favourable for profiling NP nicotine delivery and safety in human use, and for further product development. ISRCTN registry study no. ISRCTN75583947.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693475","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":"Interactions of pain and opioids on conditioned place preference in rodents.","authors":"Angela E Barattini, Amanda R Pahng","doi":"10.1007/s00213-024-06719-1","DOIUrl":"https://doi.org/10.1007/s00213-024-06719-1","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid analgesics are the most effective medications used for the treatment of pain, however there are significant risks associated with repeated opioid use including opioid misuse and opioid use disorder development. Chronic pain affects millions of adults in the United States, and opioid misuse is often comorbid with pain conditions in individuals who are repeatedly treated with opioids. In addition to providing pain relief, opioids produce rewarding effects, but in chronic pain states, reward processing can become dysregulated. The conditioned place preference task is commonly used to measure the rewarding properties of opioids in rodents. During this task, opioid administration is paired with a distinct environment through repeated conditioning and the change in an animal's preference for the paired environment indicates whether the opioid is rewarding or not.</p><p><strong>Objectives: </strong>Rodent pain models can be combined with conditioned place preference to examine the effects of pain on opioid reward. The existing preclinical literature on pain effects on conditioned place preference is conflicting, where pain conditions have been reported to enhance, suppress, or have no effect on opioid reward. This review will discuss several factors that may contribute to these discordant findings including conditioning session duration and number, rodent strain differences in opioid sensitivity, analgesic properties of opioids at tested doses, locomotor effects at tested doses, and diurnal variation in pain sensitivity. Future studies should consider how these factors contribute to opioid conditioned place preference in both pain and pain-free animals to have a better understanding of the interactions between pain and opioid reward.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676774","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":"The effect of mixed tobacco monoamine oxidase inhibitors in animal models relevant to tobacco dependence.","authors":"Penelope Truman, Diana Vivian Atigari, Meyrick Kidwell, Joyce Colussi-Mas, Bart Ellenbroek","doi":"10.1007/s00213-024-06712-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06712-8","url":null,"abstract":"<p><strong>Rationale: </strong>Tobacco monoamine oxidase (MAO) inhibitors have long been suspected of influencing tobacco dependence, but direct evidence of their effects has been difficult to obtain. Recently we have identified two new groups of monoamine oxidase inhibitors, hydroquinones and polyunsaturated fatty acids (linoleic and linolenic acid), abundant in tobacco smoke.</p><p><strong>Objectives: </strong>To test, in relevant animal models, whether the combined effect of these inhibitors is sufficient to affect addictive responses to nicotine.</p><p><strong>Methods: </strong>Here we report the first tests of the effects of mixed tobacco MAO inhibitors in three animal behavioural tests relevant to nicotine addiction, conditioned place preference, locomotor sensitisation and nicotine self-administration. Inhibitors used were the aforementioned linoleic and linolenic acid, and catechol, 4-ethylcatechol, 4-methyl catechol and hydroquinone, together with the already known inhibitors harman and norharman. They were administered together in the ratios found in tobacco smoke.</p><p><strong>Results: </strong>In conditioned place preference and in self-administration tests the addition of these tobacco MAO inhibitors significantly increased responding to nicotine and motivation to self-administer nicotine, supporting the hypothesis that inhibition of MAO enzymes in the brain enhances addictive responses such as that for nicotine. The combined MAO inhibitors without nicotine did not cause increased locomotor activity and did not induce a place conditioned response.</p><p><strong>Conclusions: </strong>Our results show that the combined effect of three groups of major MAO inhibitors present in tobacco smoke can enhance the addictive responses to nicotine in rats. There is no evidence from this study that these MAO inhibitors are addictive in themselves.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648787","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":"Efficacy and safety of prophylactic use of benzhexol after risperidone treatment in MK-801-induced mouse model of schizophrenia.","authors":"Yongjie Zhong, Wenhui Wang, Miaomiao Zhang, Yitan Yao, Huanzhong Liu, Kai Zhang","doi":"10.1007/s00213-024-06716-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06716-4","url":null,"abstract":"<p><strong>Rationale: </strong>There is a debate about whether doctors should prophylactically use benzhexol in schizophrenic patients to reduce the occurrence of extrapyramidal side effects (EPS) after risperidone treatment.</p><p><strong>Objectives: </strong>We conducted a prospective animal model to explore the efficacy and safety of the prophylactic use of benzhexol after risperidone treatment and the mechanism of the process.</p><p><strong>Methods: </strong>C57/BL mice were injected with MK-801 (0.5 mg/kg, i.p.) once a day for two weeks. The open field test (OFT) and the novel object recognition test (NORT) assessed the schizophrenia-like behavior of mice. After four weeks of treatment with benzhexol (10 mg/kg, i.g.) and risperidone (3 mg/kg, i.g.), the inclined screen test (IST), rotarod test (RT), open field test (OFT), novel object recognition test (NORT) and the Morris water maze test (MWM) were conducted successively. The expression of BDNF, p-Tau, and Tau in the hippocampus was detected by Western blot assay.</p><p><strong>Results: </strong>We showed that benzhexol can significantly attenuate risperidone-induced motor coordination impairments and catalepsy and did not affect the efficacy of risperidone in reducing spontaneous activity. Notably, the prophylactic use of benzhexol reduced the recognition memory and spatial memory in MK-801-induced model mice after risperidone. In addition, benzhexol increased the ratio of p-Tau/Tau and decreased BDNF expression levels in the hippocampus.</p><p><strong>Conclusions: </strong>We found that the prophylactic use of benzhexol can reduce the occurrence of EPS and does not affect the efficacy of risperidone in the treatment of positive symptoms. Benzhexol may impair cognitive function but did not cause further deterioration of cognitive function in MK-801 mice.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648733","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":"Endocannabinoid dysregulation and PTSD in urban adolescents: Associations with anandamide concentrations and FAAH genotype.","authors":"Hilary A Marusak, Samantha L Ely, Clara G Zundel, Leah C Gowatch, MacKenna Shampine, Carmen Carpenter, Reem Tamimi, Alaina M Jaster, Tehmina Shakir, Len May, Terri A deRoon-Cassini, Cecilia J Hillard","doi":"10.1007/s00213-024-06717-3","DOIUrl":"https://doi.org/10.1007/s00213-024-06717-3","url":null,"abstract":"<p><strong>Background: </strong>The endocannabinoid system, which regulates fear- and anxiety-related behaviors, is dysregulated in adults with posttraumatic stress disorder (PTSD), as indicated by higher circulating anandamide (AEA) concentrations. The C385A (rs324420) polymorphism in the fatty acid amide hydrolase (FAAH) gene, which catabolizes AEA, is linked to higher AEA concentrations and greater PTSD symptoms in adults. Given that adolescence is a critical period during which trauma and psychiatric disorders emerge, understanding this relationship in youth is essential. This study examines PTSD symptoms, AEA concentrations, and FAAH genotype in a diverse adolescent sample.</p><p><strong>Methods: </strong>This study included 102 Detroit-area adolescents (M ± SD = 13.33 ± 2.21 years, 54.9% female) and their parents/guardians. The sample consisted of 40.2% White Non-Hispanic, 34.3% Black Non-Hispanic, 6.9% White Hispanic, 4.9% Asian/Pacific Islander, and 12.7% Biracial adolescents. Trauma exposure and PTSD symptoms were assessed using the UCLA PTSD Reaction Index for DSM-5. Plasma concentrations of AEA were measured by liquid chromatography-tandem mass spectrometry, and FAAH genotype was determined from saliva samples and high-throughput screening.</p><p><strong>Results: </strong>The majority (90%) of adolescents reported trauma exposure, and 20% met PTSD criteria. Higher AEA concentrations were associated with more severe PTSD symptoms (p = 0.009), especially hyperarousal. The FAAH A-allele (present in 52.5% of participants) was associated with higher AEA concentrations (2.11 ± 0.69 pmol/ml, p = 0.013) and greater PTSD severity (22.65 ± 15.931, p = 0.027), particularly those with the reexperiencing cluster, compared to the CC genotype (1.79 ± 0.66 pmol/ml and 15.87 ±+ 13.043, respectively).</p><p><strong>Conclusion: </strong>Elevated AEA concentrations and the FAAH A-allele were associated with greater PTSD symptom severity in urban adolescents. These findings suggest endocannabinoid dysregulation may play a role in adolescent PTSD, highlighting the need for further research and targeted interventions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639662","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":"Behavioral studies of the abuse potential and anesthetic and sedative effects of etomidate in male rodents.","authors":"Lixin Kuai, Xiangyu Li, Deli Xu, Linggao Zeng, Peng Xu, Bin Di, Fang Yan, Dan Wang","doi":"10.1007/s00213-024-06715-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06715-5","url":null,"abstract":"<p><strong>Rationale: </strong>Etomidate is a short-acting general anesthetic for clinical use and has been used as alternative to propofol or added to the powdered drug and e-cigarette cartridges recently, leading to an increase in abuse. But there have been no studies conducted on the abuse potential of etomidate.</p><p><strong>Objectives and methods: </strong>This study aimed to evaluate the abuse potential of etomidate via conditioned place preference (CPP) and self-administration tests, reflecting its rewarding and reinforcing effects. In addition, righting reflex and open-field tests were conducted to evaluate the anesthetic and sedative effects of etomidate.</p><p><strong>Results: </strong>In male mice, the ED₅₀ after intraperitoneal (i.p.) injection of anesthetic effect for etomidate was 9.156 mg/kg and the ED₅₀ of the sedative effect 5 min after intraperitoneal injection was 2.389 mg/kg. Etomidate induced CPP in male mice at the minimum dose of 3 mg/kg i.p. and supported stable self-administration in male rats at the dose of 0.075 mg/kg/intravenous infusion. The dose-response curve of etomidate was an inverted U-shape, which showed significant self-administrations compared with the vehicle group at doses of 0.05-0.1 mg/kg/infusion etomidate and the highest intake of 21.1 ± 0.64 infusions per 4 h-session.</p><p><strong>Conclusions: </strong>These results clearly demonstrate that etomidate has rewarding and reinforcing effects in male rodents, as well as effects on anesthesia and motor inhibition. These findings indicate the possibility of abuse potential in humans using etomidate.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626861","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}