Psychopharmacology最新文献

{"title":"Cannabigerol and standardized full-spectrum cannabis extract effects in acute and chronic inflammatory pain models.","authors":"Daniela Escobar-Espinal, Thaís Antonia Alves Fernandes, Rafaela Ponciano, Lorena Borges, Bianca Andretto de Mattos, Jaime E C Hallak, Jose A Crippa, Francisco Silveira Guimarães, Elaine Del-Bel, João Francisco C Pedrazzi, Glauce Crivelaro Nascimento","doi":"10.1007/s00213-026-07156-y","DOIUrl":"https://doi.org/10.1007/s00213-026-07156-y","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory pain is associated with persistent sensory and immune dysregulation. We evaluated the therapeutic efficacy of two cannabinoids formulations-Cannabigerol (CBG) and Standardized Full-Spectrum Cannabis Extract (FULL) in a preclinical model of acute and Chronic inflammatory pain and examined their effects on peripheral and central inflammatory mediators.</p><p><strong>Methods: </strong>Cannabinoid analgesic effects were assessed in male Wistar Hannover rats using acute (formalin) and chronic inflammatory pain (CFA) models. Treatments were administered at different doses before the formalin test and after CFA as a single dose or once daily for 21 days. Motor function and inflammatory markers (TNF-α and IL-10) were evaluated using actimeter test and ELISA.</p><p><strong>Results: </strong>In the formalin test, both cannabinoids reduced nociceptive behaviors during Phase I, whereas only FULL produced sustained analgesia during Phase II. In the chronic model, single administration produced no significant effects; while repeated treatment (highest doses) improved mechanical thresholds. FULL (10 mg/kg) produced earlier analgesic effects (day 10), while CBG (10 mg/kg) fully restored baseline sensitivity from day 15 onward. In locomotor assessments, both compounds prevented CFA-induced motor impairments, except at the lowest CBG dose. CFA increased tumor necrosis factor-alpha (TNF-α) in the spinal cord, dorsal root ganglia (DRG), and plasma. Both cannabinoids prevented the CFA-induced increase in TNF-α levels in the spinal cord and plasma. Elevated TNF-α in the DRG persisted despite treatment, indicating region-specific regulation. Interleukin-10 (IL-10) levels were unaffected.</p><p><strong>Conclusion: </strong>Both cannabinoids exert analgesic and anti-inflammatory effects, with FULL providing faster acute relief and CBG produced a more prolonged antinociceptive effect.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888479","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":"Divergent effects of ketamine and psilocybin on EEG power spectral density in a mismatch negativity paradigm.","authors":"Milad Soltanzadeh, Zheng Wang, Shona G Allohverdi, Colleen E Charlton, André Schmidt, Franz X Vollenweider, Andreea O Diaconescu","doi":"10.1007/s00213-025-06952-2","DOIUrl":"10.1007/s00213-025-06952-2","url":null,"abstract":"<p><strong>Rationale: </strong>Ketamine and psilocybin have demonstrated therapeutic potential for mental disorders, including major depressive disorder, yet they engage distinct mechanisms of action. Ketamine, a dissociative hallucinogen, acts by blocking N-methyl-D-aspartate receptors (NMDAR), whereas psilocybin primarily targets serotonin receptors. These divergent mechanisms are reflected in their electrophysiological biomarkers.</p><p><strong>Objectives: </strong>This study aimed to investigate the divergent effects of ketamine and psilocybin on different elements of the EEG frequency spectrum, focusing on aperiodic components as an indicator of excitation-inhibition balance in the neural circuitry.</p><p><strong>Methods: </strong>We re-analyzed a previously acquired EEG dataset from healthy volunteers using a placebo-controlled within-subject crossover design (Schmidt et al., Neuropsychopharmacology 37(4):865-875 2012). Participants received either placebo or S-ketamine (N=19) and placebo or psilocybin (N=16) during an auditory roving paradigm. Spectral parameters including periodic and aperiodic were extracted and partial least squares analysis was employed.</p><p><strong>Results: </strong>Ketamine significantly altered the offset and slope of the EEG spectrum, suggesting a disruption in excitatory-inhibitory balance. While both drugs commonly reduced alpha power in similar regions, beta band activity was decreased exclusively under ketamine.</p><p><strong>Conclusions: </strong>These findings highlight ketamine's unique effects on aperiodic EEG components, reinforcing its role as a neurochemical model of prodromal psychosis. Psilocybin's effects appear distinct, emphasizing its targeted influence on oscillatory activity.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2069-2083"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445569","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":"Retraction Note: Matrine alleviates neurobehavioral alterations via modulation of JNK-mediated caspase-3 and BDNF/VEGF signaling in a mouse model of burn injury.","authors":"Adnan Khan, Bushra Shal, Muhammad Naveed, Bakht Nasir, Nadeem Irshad, Hussain Ali, Salman Khan","doi":"10.1007/s00213-026-07142-4","DOIUrl":"10.1007/s00213-026-07142-4","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2221"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689861","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":"Sex-dependent therapeutic effects of nano-curcumin on alzheimer's disease: enhanced cognitive and physiological restoration in female mice.","authors":"Karline da Costa Rodrigues, Meliza da Conceição Oliveira, Isadora Cielo de Souza, Andreza Wachholz Igansi, Ana Vitória Barbosa Lopes, Camila de Oliveira Pacheco, Sandra Elisa Hass, Ricardo Frederico Schumacher, Cristiane Luchese","doi":"10.1007/s00213-025-06967-9","DOIUrl":"10.1007/s00213-025-06967-9","url":null,"abstract":"<p><p>Curcumin (Cur) is a bioactive compound with neuroprotective and anti-inflammatory effects, though its clinical application is limited by poor bioavailability. This study assessed the impact of nanocapsulated curcumin (NcCur), formulated Eudragit (EUD) polymer, in a sporadic Alzheimer's disease (AD) mouse model induced by intracerebroventricular streptozotocin (STZ), with attention to sex-specific differences. Mice received STZ (3 nmol/3 µL) or 0.9% saline on days 1 and 3, followed by intragastric treatment with Cur or NcCur (10 mg/kg, on alternate days) from day 22 until euthanasia - a dose previously shown to be effective in behavioral and biochemical modulation in rodent models of neurodegeneration. Behavioral assessments included open field, elevated plus maze (EPM), tail suspension (TST), object recognition, Y-maze, and step-down avoidance tasks (SDAT), performed before and after treatment. After euthanasia, thymus, spleen and adrenal glands were weighed; biochemical assays evaluated oxidative stress, monoaminergic and cholinergic enzymes, and Na⁺K⁺-ATPase activity. NcCur improved short- and long-term memory in both sexes, with greater effects in females (42% and 35%) than males (28% and 25%). In the EPM, NcCur increased open arm time more prominently in females (40%) than males (25%), while TST immobility time was reduced similarly in both. Spatial and aversive memory improved in both sexes, but females showed greater performance in the SDAT. Biochemical analyses showed reductions in reactive species in males (45%) and females (55%) with NcCur; Na⁺K⁺-ATPase activity increased in females (60%) and males (50%). AChE activity was restored in both sexes. NcCur reduced MAO-A/B activities more in females (65%/55%) than in males (45%/35%). Thymus and spleen weights were normalized in both sexes, with stronger effects in females. NcCur also mitigated alterations in thymus and spleen relative weights, suggesting immunomodulatory effects. Some biochemical and behavioral responses were more prominent in females, both sexes benefited from treatments. These findings suggest that NcCur enhances Cur therapeutic potential through multimodal actions linked involving modulation of oxidative stress, cholinergic and monoaminergic systems, and immune-related parameters. NcCur emerges as a promising candidate for AD-like intervention in both sexes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2185-2204"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588491","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":"Ketamine attenuates anxiety-like behavior and oxidative imbalance in the maternal immune activation model: emphasis on the cerebellum.","authors":"Elifrances Galdino de Oliveira, Mayara Victória de Souza Barbosa, Diógenes Afonso de Lima, José Carlos da Silva Júnior, Severina Cassia de Andrade Silva, Jonata Henrique de Santana, Osmar Henrique Dos Santos Júnior, Eduardo Carvalho Lira, Claudia J Lagranha, Filipe Silveira Duarte, Dayane Aparecida Gomes","doi":"10.1007/s00213-025-06974-w","DOIUrl":"10.1007/s00213-025-06974-w","url":null,"abstract":"<p><strong>Rationale: </strong>Relevant to the study of neurodevelopmental disorders, maternal immune activation (MIA) models reproduce the high incidence of anxiety disorders and molecular alterations in the cerebellum reported in patients with schizophrenia and autism. In parallel, ketamine, a fast-acting antidepressant, has shown beneficial effects in psychiatric disorders with immune-related components.</p><p><strong>Objectives: </strong>To investigate anxiety-like behavior, inflammatory status, and oxidative balance in the cerebellum of offspring exposed to MIA and to test the potential effects of ketamine postnatal treatment in reversing the behavior and molecular changes.</p><p><strong>Methods: </strong>To induce MIA, pregnant Swiss mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS; 100 µg/kg/day) or saline (10 mL/kg/day) on gestation days 15 and 16, and subsequently, male offspring were administered saline (10 mL/kg/day) or ketamine (20 mg/kg/day) from postnatal day 36 to 50. On postnatal day 62, the offspring were assessed for anxiety-like behavior, and the cerebellum was collected for analysis of IL-1β, IL-6, TGF-β, and TNF-α gene expression and oxidative balance.</p><p><strong>Results: </strong>Our results demonstrated that MIA increased anxiety-like behavior in offspring, accompanied by an increase in TNF-α expression, and oxidative imbalance in the cerebellum. Ketamine administration reversed the anxiety-like behavior, as well as attenuated both TNF-α expression and oxidative imbalance.</p><p><strong>Conclusions: </strong>Our findings suggest that the cerebellum is an important site of long-lasting changes induced by MIA and a relevant target of ketamine's effects. These results highlight the cerebellum's role in pathophysiological processes and its potential as a site for therapeutic intervention in psychiatric disorders.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2205-2219"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638064","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":"Intact neurophysiological markers of death denial in long-term ayahuasca users.","authors":"Yair Dor-Ziderman, Jonathan David, Aviva Berkovich-Ohana","doi":"10.1007/s00213-025-06963-z","DOIUrl":"10.1007/s00213-025-06963-z","url":null,"abstract":"<p><strong>Rationale: </strong>There is growing enthusiasm around the potential of psychedelics to transform how individuals engage with the theme of death, with self-report evidence suggesting these substances foster acceptance and reduce fear-of-death. Yet, given extensive evidence linking unconscious processes to mortality avoidance, current research efforts remain limited and call for implicit and neurobiology-based measures.</p><p><strong>Objectives & methods: </strong>To this end, we applied a validated no-report magnetoencephalogram (MEG) visual MisMatch Response (vMMR) paradigm to assess whether long-term ayahuasca users (N = 50), compared to previously published data from healthy controls and experienced meditators, show self-specific neurophysiological markers of death-denial/acceptance. Self-report and behavioral measures of fear-of-death were also collected.</p><p><strong>Results: </strong>Cluster-based permutation analyses on the vMMR data showed that ayahuasca users' brains responded to the coupling of death and self-stimuli in a manner indicating denial rather than acceptance. At the same time, 1-way ANOVAs and post hoc t-tests analyses indicated that the ayahuasca group evidenced less implicit fear-of-death than the general population, and less explicit fear-of-death than both the general and meditator samples. Further correlation analyses on the neurophysiological ayahuasca sample death-denial marker supported its construct validity by associating it with less self-reported death acceptance and reduced accessibility to death-related thoughts. Finally, death-denial was linked to greater life satisfaction, supporting its adaptive role.</p><p><strong>Conclusions: </strong>These findings provide preliminary evidence that while ayahuasca may alter how humans interact with the theme of death on conceptual and affective levels of cognitive processing, on automatic, perceptual unconscious levels of self-specific processing, death-denial processes appear to remain intact.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2165-2183"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482916","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":"Methylphenidate and sustained attention in rats: a systematic review.","authors":"Adela Batanero-Geraldo, Fátima Montiel-Herrera, Juan Carlos López, Juan Pedro Vargas","doi":"10.1007/s00213-026-07007-w","DOIUrl":"10.1007/s00213-026-07007-w","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2005-2018"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181842","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":"Investigating antidiabetic drug targets as potential therapeutic modulators for schizophrenia.","authors":"Yu-Sheng Huang, Xu Lin, Ya-Juan Xu, Gui-Bing Chen","doi":"10.1007/s00213-025-06951-3","DOIUrl":"10.1007/s00213-025-06951-3","url":null,"abstract":"<p><strong>Rationale: </strong>Certain types of antidiabetic drugs (ADs) have been proven to improve cognitive functions and symptom dimensions in schizophrenia (SCZ).</p><p><strong>Objectives: </strong>Schizophrenia is a major contributor to social functional impairment, and antipsychotics (APs) remain the cornerstone of its treatment. Investigating the potential of antidiabetic drugs as APs could significantly advance therapeutic strategies for schizophrenia.</p><p><strong>Methods: </strong>To assess this potential, we employed an integrated analytical framework that included two-sample Mendelian randomization (MR) using genetic proxies for antidiabetic drug targets, multivariable MR (MVMR), and colocalization analyses. Furthermore, gene and drug enrichment analyses alongside molecular docking studies were performed to elucidate underlying mechanisms and identify candidate drugs. The analysis utilized summary statistics from genome-wide association meta-analyses (GWAS) of schizophrenia, as well as gene expression data from the eQTLGen consortium.</p><p><strong>Results: </strong>A total of fourteen drug targets were identified among eight major antidiabetic drugs. Notably, RXRB, a target of thiazolidinediones (TZDs), exhibited a strong inverse association with schizophrenia risk (OR: 0.28, 95% CI: 0.21-0.38, P < 0.001). Other significant targets included GPD1 (targeted by metformin), LRP2 (insulin), SLC5A2 (SGLT2 inhibitors), and ABCC8/KCNJ11 and INS (sulfonylureas). Primary and secondary MR analyses confirmed the associations of RXRB, INS, LRP2, and SLC5A2 with gene expression levels. Drug enrichment and molecular docking analyses identified bezafibrate as a promising candidate for repurposing as an AP.</p><p><strong>Conclusion: </strong>Antidiabetic drugs may possess therapeutic potential in schizophrenia by modulating specific drug-related pathways.These findings provide new theoretical support for the selection of ADs in patients with schizophrenia comorbid with diabetes, and also offer new insights for the future development of APs.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2055-2067"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482929","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":"Comparison between a chimeric anti-methamphetamine monoclonal antibody and humanized antibodies on pharmacological effects of methamphetamine.","authors":"Michael Dale Berquist, Melinda Gunnell, Ralph Henry, William Brooks Gentry, Misty Ward Stevens","doi":"10.1007/s00213-025-06959-9","DOIUrl":"10.1007/s00213-025-06959-9","url":null,"abstract":"<p><strong>Rationale: </strong>Individuals with methamphetamine use disorder (MUD) can experience significant suffering due to the harmful effects of methamphetamine (METH) on physical and mental health. Although there are no approved medications for MUD, immunotherapies, including monoclonal antibodies (mAb), could serve as treatments for this debilitating condition. Our candidate anti-METH mAb called \"devextinetug\" features a mouse-derived variable binding region called \"7F9\" and a humanized constant domain. Our earlier work has shown that devextinetug is effective in altering METH's pharmacological effects. However, it is unknown whether the effectiveness of a chimeric mAb would be altered, or possibly improved, if the variable region were humanized. Moreover, no studies have determined whether onset and offset rates of binding to METH predicts anti-METH effectiveness of mAb candidates.</p><p><strong>Objectives: </strong>The goals of the present study were to compare the anti-METH effectiveness of a chimeric mAb (called \"IS12\") that features our parental 7F9 variable region with a panel of mAbs that have fully humanized variable regions, and to determine whether onset and/or offset rates of binding to METH are associated with anti-METH effectiveness.</p><p><strong>Methods: </strong>We humanized the variable region from ch-mAb7F9 with multiple sequences to produce 48 IgGs. The on and off rates to METH binding were determined for these IgGs and, based on their various onset/offset rats, we chose eight candidate IgGs for further testing (including our parental IS12). All eight IgGs were tested for ligand cross-reactivity and in a METH-elicited locomotor stimulation model in rats.</p><p><strong>Results: </strong>Cross-reactivity results revealed that IS12 exhibited the greatest affinity to METH, and it also produced the largest reduction in METH-elicited locomotor stimulation compared to the other seven candidates. Furthermore, onset and offset rates of binding to METH did not appear to be associated with reducing METH's in vivo pharmacological effects.</p><p><strong>Conclusions: </strong>The 7F9 variable region is the most promising to treat MUD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2131-2141"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744165","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 TPA023B, an α2/3/5GABA_A subtype-selective partial allosteric modulator, on fentanyl-induced respiratory depression in male rats: comparison with the non-selective benzodiazepine midazolam.","authors":"Loc M Pham, Andria B Nanney, Jordan Hasting, Daniela Rüedi-Bettschen, Kevin B Freeman, James K Rowlett","doi":"10.1007/s00213-025-06945-1","DOIUrl":"10.1007/s00213-025-06945-1","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid-related overdose deaths involving benzodiazepines have increased in recent years, and prior studies have reported that clinically used benzodiazepines can enhance the respiratory-depressant effects of mu opioid receptor (MOR) agonists. TPA023B is an α1-sparing GABA_A positive allosteric modulator developed as a potential anxiolytic with fewer benzodiazepine-typical side effects. However, it is unknown if and to what degree TPA023B can affect MOR-agonist induced respiratory depression.</p><p><strong>Objectives: </strong>The current study compared the effects of either TPA023B or midazolam, alone and combined with fentanyl, on respiratory depression in rats, using whole-body plethysmography.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were implanted with chronic indwelling intravenous (i.v.) catheters for drug infusions. Respiration (frequency, tidal volume, and minute volume) was measured using whole-body plethysmography. The tests consisted of a pretreatment (midazolam, 30 mg/kg; i.v.; TPA023B, 1.0 mg/kg; i.v; or vehicle) followed by a fentanyl injection (0.01, 0.03, 0.1 mg/kg, i.v., or vehicle) and 60 min of respiration assessment.</p><p><strong>Results: </strong>Overall, fentanyl alone, but not TPA023B or midazolam alone, produced dose-dependent reductions in tidal volume and minute volume. When administered as pre-treatments, neither midazolam nor TPA023B increased the magnitude of fentanyl-induced respiratory depression, instead producing prolonged reductions in tidal volume and minute volume. Midazolam produced a more sustained reduction in these parameters than TPA023B.</p><p><strong>Conclusions: </strong>Benzodiazepines prolong fentanyl-induced respiratory depression, but this effect may be reduced by eliminating activity at α1GABA_A receptor subtypes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2019-2028"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422584","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}