Psychopharmacology最新文献

{"title":"Enantiomer-specific modulation of GABA_A receptors differentially regulates stress-induced dopamine dysregulation.","authors":"Kayla Lilly, Prithu Mondal, James M Cook, Stephanie M Perez, Daniel J Lodge","doi":"10.1007/s00213-026-07164-y","DOIUrl":"https://doi.org/10.1007/s00213-026-07164-y","url":null,"abstract":"<p><strong>Rationale: </strong>Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that can emerge following exposure to severe trauma and is frequently accompanied by comorbid psychiatric symptoms, including psychosis. Hallucinations and delusions associated with PTSD are thought to arise from dysregulated mesolimbic dopamine signaling; however, converging evidence indicates dopamine dysfunction is secondary to hippocampal hyperactivity driven by impaired GABAergic transmission. An emerging pharmacological strategy is the use of positive allosteric modulators (PAMs) of GABA_A receptors. Given their dense expression within the hippocampus, receptors containing the α5 subunit (α5-GABA_ARs) have demonstrated antipsychotic-like efficacy across multiple preclinical models.</p><p><strong>Objectives: </strong>Whether this therapeutic potential reflects α-subunit specificity or broader properties of structurally related PAMs remains unclear. We compared three structurally related GABA_A receptor PAMs with distinct α-subunit selectivity.</p><p><strong>Methods: </strong>Using an acute inescapable footshock stress model, which reliably produces increased mesolimbic dopamine activity, we performed in vivo extracellular electrophysiology to record dopamine neuron activity in the ventral tegmental area (VTA) after intra-hippocampal administration of GABA_AR PAMs.</p><p><strong>Results: </strong>MP-III-022, a selective α5-GABA_AR PAM, normalized stress-induced elevations in VTA dopamine neuron population activity, consistent with prior reports. GL-I-54, which preferentially modulates α2/α3-GABA_ARs, failed to restore dopamine system function following stress, while modulation with the α5-preferring enantiomer GL-II-73 was associated with normalization of mesolimbic dopamine activity.</p><p><strong>Conclusions: </strong>These findings indicate that stereochemical and subunit-selective modulation of GABA_A receptors critically determines circuit-level outcomes following stress and reinforce α5-GABA_A receptors as a key target for normalizing hippocampal-driven dopamine system dysfunction associated with psychosis-relevant states.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945602","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":"Concurrent chronic methamphetamine exposure may influence behavioral outcomes following repetitive mild traumatic brain injury.","authors":"Nicole M Hall, Peter H Seidenberg, Nicholas E Goeders","doi":"10.1007/s00213-026-07162-0","DOIUrl":"https://doi.org/10.1007/s00213-026-07162-0","url":null,"abstract":"<p><strong>Rationale: </strong>Traumatic brain injury (TBI) and substance use disorder (SUD) share several characteristics, including neurological outcomes and pathological traits. Misuse of stimulants, both non-prescription use of medications and illicit use of methamphetamine, is rising. Despite potential for misuse, stimulants are prescribed as treatment for some TBI-induced symptoms. Given that 40% of TBI patients have a history of SUD prior to injury, studies of the role that chronic substance misuse plays on the deleterious outcomes of TBI are warranted.</p><p><strong>Objectives: </strong>Our study explores the role that chronic methamphetamine exposure plays in the acute and long-term behavioral outcomes of repetitive mild TBI (rmTBI). We hypothesized that chronic methamphetamine exposure would exacerbate the behavioral deficits induced by rmTBI.</p><p><strong>Methods: </strong>We developed a model combining non-contingent dosing of methamphetamine with the Closed Head Model of Engineered Rotational Acceleration (CHIMERA). Behavioral assays were employed one month after the final TBI to assess short-term effects and were repeated six months following the final TBI for long-term effects.</p><p><strong>Results: </strong>The Loss of Righting Reflex showed that chronic methamphetamine exposure impacted neither TBI severity nor immediate recovery. The T-maze and NORT revealed that rmTBI concurrent to chronic methamphetamine exposure induced short- and long-term cognitive deficits. Methamphetamine negatively impacted balance and coordination on the accelerated rotarod at the later timepoint only.</p><p><strong>Conclusions: </strong>Together, these findings suggest that chronic methamphetamine exposure could potentially increase long-term, but not acute, TBI-induced deficits.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920928","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":"Neuropharmacology of levamisole and its phase I metabolites: lack of evidence for levamisole-cocaine interactions.","authors":"Dorota Zolkowska, Kurt R Lehner, John S Partilla, Bruce E Blough, Michael H Baumann","doi":"10.1007/s00213-026-07145-1","DOIUrl":"10.1007/s00213-026-07145-1","url":null,"abstract":"<p><strong>Rationale: </strong>The anthelmintic agent, levamisole, is a cocaine adulterant that causes serious adverse effects in humans. A number of hypotheses have been proposed to explain why levamisole is used as an adulterant. Here, we examined whether levamisole might enhance acute pharmacological effects of cocaine.</p><p><strong>Methods: </strong>Levamisole and its phase I metabolites were tested for in vitro activity at monoamine receptors and transporters. The effect of levamisole (0.1-10 µM) on cocaine-induced inhibition of [³H]dopamine uptake was examined in rat brain synaptosomes. In vivo microdialysis in nucleus accumbens of male rats was employed to determine neurochemical effects of cocaine (1-3 mg/kg, intravenous), in the absence or presence of levamisole (1:1 ratio with cocaine).</p><p><strong>Results: </strong>Levamisole displayed no measurable activity at monoamine receptors or transporters. The metabolite aminorex acted as a potent substrate at transporters for dopamine, norepinephrine and serotonin, whereas rexamino had affinity for adrenoreceptors and weak substrate activity at norepinephrine transporters. Levamisole did not alter cocaine-induced inhibition of dopamine uptake in vitro. Administration of cocaine, or cocaine plus levamisole, produced similar increases in extracellular dopamine and locomotor stimulation in vivo.</p><p><strong>Conclusions: </strong>We found no evidence that levamisole alters the acute pharmacological effects of cocaine in male rats. The metabolite aminorex is a potent monoamine transporter substrate which could contribute to effects of levamisole under certain conditions (e.g., repeated, high-dose exposure), but most studies in human users of levamisole-adulterated cocaine have failed to detect measurable quantities of aminorex.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920880","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":"Learning and memory performance in a rat model of perigestational opioid exposure.","authors":"Meghan E Vogt, Anne Z Murphy","doi":"10.1007/s00213-026-07160-2","DOIUrl":"10.1007/s00213-026-07160-2","url":null,"abstract":"<p><strong>Rationale: </strong>Nearly one third of women of reproductive age in the United States are prescribed opioids annually; 14% will fill an opioid prescription during pregnancy, and one in five report misuse. Opioid use during pregnancy has given rise to an increasing population of infants born with gestational opioid exposure. At school age, these children show neurodevelopmental impairment and higher rates of learning disabilities.</p><p><strong>Objectives: </strong>To characterize how exposure to exogenous opioids during brain development affects learning and memory performance, our lab has developed a rat model of perigestational opioid exposure that closely recapitulates a clinically relevant dosing timeline by beginning morphine exposure before pregnancy and continuing through the first postnatal week.</p><p><strong>Methods: </strong>Male and female offspring generated from this model were assessed on several facets of learning and memory during adolescence.</p><p><strong>Results: </strong>Here, we report that morphine exposure selectively impaired spatial learning, as measured by the Barnes Maze, and associative learning, as measured by an Attentional Set Shift Task, without significantly impacting working or short-term memory. Environmental enrichment rescued the spatial learning deficit in males but not females.</p><p><strong>Conclusion: </strong>Our findings suggest that gestational opioid exposure can impair performance in complex cognitive tasks, and non-invasive, non-pharmacological intervention may attenuate these deficits.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913241","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":"Calcium-permeable AMPA receptors contribute to the accelerated development of enhanced motivation for cocaine in female rats.","authors":"Eleanor Blair Towers, Ivy L Williams, Emaan I Qillawala, Ben Setaro, Kyle A Hsu, Wendy J Lynch","doi":"10.1007/s00213-026-07146-0","DOIUrl":"10.1007/s00213-026-07146-0","url":null,"abstract":"<p><strong>Rationale: </strong>The telescoping effect, where females progress more rapidly than males from initial drug use to developing a substance use disorder, is a widely cited sex/gender difference, yet its molecular basis remains unknown.</p><p><strong>Objectives: </strong>To test whether calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc) contribute to the development of enhanced motivation for cocaine, a defining feature of addiction, which emerges earlier in females than in males.</p><p><strong>Methods: </strong>Motivation for cocaine was measured under a progressive-ratio schedule before and after extended-access self-administration (4 trials/h, 24 h/day, 10 days) and a 7-day abstinence period. During abstinence, females received SYN119 (0 or 10 mg/kg) to block, and males received JNJ16259685 (0 or 5 mg/kg) to enhance, NAc CP-AMPAR recruitment, consistent with a hypothesis-driven, sex-informed design. After stable motivation was established, intra-NAc infusions of the CP-AMPAR antagonist naspm (40 µg/side) were administered.</p><p><strong>Results: </strong>Females, but not males, developed enhanced cocaine motivation after 7 days of abstinence, replicating the telescoping effect. This effect was persistently blocked by SYN in females and reproduced in males by JNJ treatment for over three weeks. Subsequently, intra-NAc naspm reduced motivation in JNJ-treated males, but not SYN-treated females, supporting a role for CP-AMPARs in the development of an enhanced motivation for cocaine.</p><p><strong>Conclusion: </strong>These findings suggest that CP-AMPAR recruitment in the NAc, a mechanism classically linked to the incubation of cocaine craving, may also contribute to abstinence-dependent increases in drug motivation that emerge earlier in females.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901062","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":"Robust effects of food deprivation as a relapse trigger: comparison to other stressors, and investigation of predictive individual traits in male and female rats.","authors":"Jordan Charles, Catarina Borges, Elisabeth Sylvain, Nour Quiteshat, Uri Shalev","doi":"10.1007/s00213-026-07159-9","DOIUrl":"https://doi.org/10.1007/s00213-026-07159-9","url":null,"abstract":"<p><p>Acute food-deprivation stress causes relapse to heroin seeking in male rats following punishment-invoked abstinence. Here we tested the generality of the effect by investigating whether forced swim, footshock, or restraint stressors would induce relapse to heroin seeking in male and female rats. In addition, we assessed whether individual traits could predict stress-induced relapse. Rats were first assessed in sucrose preference (SP) test, elevated plus maze (EPM), open field test (OF), and tail-flick (TF) test. Next, rats were trained to self-administer heroin (0.1 mg/kg/infusion, 6 h/day) under a seek-take chain schedule for at least 14 days. Heroin seeking was then punished with footshock (30% of trials; 0.2-0.6 mA) for 8 days. Once the rats achieved the abstinence criterion they were exposed to a stress condition [males: restraint (30 min), forced swim (20 min), intermittent footshock (0.5 mA, 10 min) or food deprivation (24 h); females: restraint (60 min), forced swim (4 min), or food deprivation (24 h)] before undergoing a heroin-seeking test. Female rats reached abstinence faster when heroin seeking was punished. Surprisingly, only food deprivation reliably induced relapse, and patterns of stress-induced relapse were similar in male and female rats. Individual differences in traits of sweet-solution preference, anxiety, novelty exploration or nociception did not reliably predict drug relapse. Our findings demonstrate the robustness of food deprivation stress as a trigger for relapse compared to the other stressors that were applied in this study.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892269","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":"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}