Psychopharmacology最新文献

{"title":"Is it safe-and ethical-to prescribe THC to youth?","authors":"José Alexandre S Crippa, Jaime E C Hallak","doi":"10.1007/s00213-026-07186-6","DOIUrl":"https://doi.org/10.1007/s00213-026-07186-6","url":null,"abstract":"<p><p>The medical use of cannabis-derived products in children and adolescents has expanded beyond established indications for purified cannabidiol (CBD), with increasing investigation of CBD-rich extracts containing Δ9-tetrahydrocannabinol (THC) for neuropsychiatric conditions. Although preliminary studies suggest potential symptomatic benefits, the evidence remains limited by small samples, heterogeneous formulations, short follow-up, and insufficient assessment of long-term neurodevelopmental outcomes. Unlike CBD, THC directly activates CB1 receptors as a partial agonist, a pharmacological property underlying both its therapeutic and psychoactive effects. Following oral administration, THC undergoes extensive first-pass metabolism to the psychoactive metabolite 11-hydroxy-THC, with substantial interindividual variability in pharmacokinetics and pharmacodynamics supporting individualized dosing according to clinical response and tolerability. Experimental studies raise concerns regarding THC exposure during neurodevelopment, while observational studies associate frequent, high-potency recreational cannabis use with cognitive impairment, psychosis, and other adverse psychiatric outcomes. These findings cannot be directly extrapolated to regulated medicinal cannabinoid use, which differs substantially in product composition, dosing, administration, therapeutic indication, and clinical monitoring. Nevertheless, long-term neurodevelopmental safety data for medicinal THC exposure in children and adolescents remain limited. These uncertainties must be weighed against the consequences of inadequately treated disease, particularly severe drug-resistant epilepsy. Accordingly, the risk-benefit assessment of THC-containing products should be individualized, considering disease severity, treatment refractoriness, available evidence-based alternatives, therapeutic response, and tolerability. Long-term prospective studies and improved patient-selection strategies are needed to better define the role of THC-containing medicinal products in pediatric populations.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184200","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":"Acute anxiogenic effects of psilocybin and the related tryptamine, norbaeocystin, in male and female rats.","authors":"Marisa J Savini, Kylie M King, Lillianna P Puppel, Aleece K Al-Olimat, Noelle M Molnar, Evelynn J Schneider, Savannah E Straub, Joe Parker, Colin J Gottron, Allison M Bach, Solomon M Lambdin, Stephanie M Regan, Kaitlyn E Williams, Troy R Welker, J Andrew Jones, Phillip R Zoladz","doi":"10.1007/s00213-026-07188-4","DOIUrl":"https://doi.org/10.1007/s00213-026-07188-4","url":null,"abstract":"<p><strong>Rationale: </strong>Psychedelics are considered to be promising therapeutic agents that could effectively treat several psychological disorders. However, these compounds can exert acute adverse effects that limit their practicality.</p><p><strong>Objectives: </strong>Across three experiments, the present study examined the acute and delayed effects of psilocybin (PSIL) and its putatively non-hallucinogenic analog, norbaeocystin (NOR), on anxiety-like behavior and the influence of the female estrous cycle on acute response to the compounds.</p><p><strong>Methods: </strong>In Experiment 1, rats were treated with PSIL or NOR (0.3-1 mg/kg) and tested on the elevated plus maze (EPM) or open field 30 min later. In Experiment 2, male and female rats were treated with 1 mg/kg PSIL or NOR and tested on the EPM 24 h later. In Experiment 3, we tracked the female estrous cycle to determine whether it was associated with the acute effects of PSIL or NOR on EPM behavior and the acoustic startle response (ASR).</p><p><strong>Results: </strong>In Experiment 1, both PSIL and NOR exerted acute anxiogenic effects in males, while only the highest dose of PSIL increased anxiety-like behavior in females. In Experiment 2, neither PSIL nor NOR impacted EPM behavior the next day. In Experiment 3, PSIL, but not NOR, had acute anxiogenic effects on EPM behavior, effects that were independent of estrous stage. Females treated with PSIL during diestrus exhibited some signs of greater ASR habituation.</p><p><strong>Conclusions: </strong>PSIL and NOR exerted transient dose- and sex-specific effects on anxiety-like behavior, which may inform their use as novel therapeutics.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184163","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":"Drug repurposing of riluzole attenuates acquisition, accelerates extinction, and prevents reinstatement of ethanol-induced conditioned place preference.","authors":"Andleeb Shahzadi, Oruc Yunusoglu, Meliha Kara, Robert D E Sewell","doi":"10.1007/s00213-026-07178-6","DOIUrl":"https://doi.org/10.1007/s00213-026-07178-6","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder (AUD) is associated with persistent drug-related memories that lead to relapse. Glutamatergic dysregulation plays a critical role in the acquisition, extinction, and reinstatement of alcohol. Riluzole, a glutamate-modulating agent, has been suggested to influence these processes; however, its effects on ethanol-related contextual learning are not fully defined.</p><p><strong>Methods: </strong>Male Swiss albino mice (25-30 g) were used in a biased conditioned place preference (CPP) model to evaluate the effects of riluzole on ethanol-induced acquisition, extinction and reinstatement in mice. Animals were conditioned with ethanol (2.0 g/kg, i.p). Riluzole (3, 10, or 30 mg/kg, i.p.) was given 30 min before ethanol administration. Extinction and reinstatement phase was conducted by using separate cohort. The ability of riluzole to prevent reinstatement was then assessed using a low priming dose of ethanol (0.5 g/kg, i.p.). CPP was quantified as the time spent in the drug-paired compartment.</p><p><strong>Results: </strong>Ethanol produced a strong CPP and confirmed the successful acquisition of drug-context associations. Riluzole did not significantly alter acquisition at low doses (3 and 10 mg/kg), but a modest effect was observed at the highest dose (30 mg/kg). During extinction, riluzole facilitated a time-dependent reduction in CPP. Riluzole 10 and 30 mg/kg, increased extinction learning. In the reinstatement phase, ethanol pre-treatment significantly induced CPP, whereas riluzole reduced this effect at 10 and 30 mg/kg and showed no significant reducing effect at 3 mg/kg.</p><p><strong>Conclusions: </strong>Riluzole attenuated ethanol-induced CPP, facilitated extinction, and reduced reinstatement in a dose and phase-dependent manner. These findings demonstrate that riluzole influences multiple phases of ethanol-associated conditioned behavior and support its further investigation as a potential pharmacological strategy for alcohol use disorder.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184175","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":"Appetitive Pavlovian conditioned approach to reward location is reduced by both adrenergic and NMDA receptor antagonism at memory reconsolidation.","authors":"Jonathan L C Lee","doi":"10.1007/s00213-026-07182-w","DOIUrl":"https://doi.org/10.1007/s00213-026-07182-w","url":null,"abstract":"<p><strong>Rationale: </strong>Appetitive Pavlovian cues can drive maladaptive reward seeking via stimulus-reward memories. Disrupting memory reconsolidation offers a potential strategy to reduce their influence, but evidence for β-adrenergic blockade with propranolol is inconsistent across behavioural paradigms, particularly relative to NMDA receptor antagonism.</p><p><strong>Objectives: </strong>We tested whether propranolol disrupts reconsolidation of appetitive sucrose memories in a paradigm involving discriminative pavlovian conditioned approach to the reward location, and compared its effects with those of the most commonly used NMDA receptor antagonist, MK-801.</p><p><strong>Methods: </strong>Adult Lister hooded rats underwent discriminative Pavlovian conditioning. Thirty minutes before a brief memory reminder (non-reinforced or reinforced), rats received systemic drug treatment or saline control. In study 1, MK-801 (0.1 mg/kg) was administered to male rats. In study 2, propranolol (10 mg/kg) was administered to equal numbers of male and female rats. Discriminative approach to the reward location was tested drug-free at 1 and 8 days.</p><p><strong>Results: </strong>In study 1, MK-801 impaired subsequent discriminated responding at test. These effects were observed not only when reminder was non-reinforced as in previous successful demonstrations, but also with reinforced reminder. In study 2, Propranolol also impaired subsequent conditioned approach, regardless of reminder type, and the effects were consistent across sexes.</p><p><strong>Conclusions: </strong>Propranolol and MK-801 can both disrupt reconsolidation of appetitive pavlovian memories under conditions that promote memory destabilisation. These findings demonstrate that β-adrenergic blockade can impair appetitive memory reconsolidation in a paradigm of conditioned approach to the reward location, challenging prior null findings and revitalising the potential for propranolol-based interventions in maladaptive reward-seeking behaviours.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138112","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":"Time-based prospective memory impairment in adults who smoke: the role of internal and external attention and cue-based intervention.","authors":"Yunfei Guo, Hui Sun, Qianhui Xing, Xinran Chen, Jiaqun Gan, Yimin Li","doi":"10.1007/s00213-026-07176-8","DOIUrl":"https://doi.org/10.1007/s00213-026-07176-8","url":null,"abstract":"<p><strong>Rationale: </strong>Long term smoking can cause sustained damage to time-based prospective memory (TBPM). However, the specific processing mechanism of smoking induced TBPM damage is not yet clear, and there is a lack of effective intervention measures.</p><p><strong>Objectives: </strong>This study systematically explores the mechanism of smoking's impact on TBPM from attention perspective and suggests its improvement effect METHODS: The experiment adopted a dual task paradigm, randomly dividing 76 adults who smoke (with a smoking history of 2-5 years and smoking more than 10 cigarettes per day) into a smoking non-reminder group and a smoking reminder group, and recruiting 32 non-smokers as a non-smoking group.</p><p><strong>Results: </strong>The results showed that the accuracy of TBPM in the smoking non-reminder group was significantly lower than that in both the smoking reminder group and the non-smoking group, and was also accompanied by lower time‑monitoring effectiveness. The smoking non-reminder group had the highest frequency of time checking, followed by the non-smoking group, and the smoking reminder group had the lowest.</p><p><strong>Conclusions: </strong>These findings suggest that adults who smoke present a dual deficit characterized by insufficient internal attention and reduced external attention effectiveness. However, reminders can effectively improve the TBPM performance of adults who smoke by reducing the demands of internal attention.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114297","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":"Co-use of cannabis and tobacco in the same occasion: Acute effects. A systematic review.","authors":"Jingqi Xu, Adrien Nette, Christina Zakala, Sampson Zhao, Justin Matheson, Christine M Wickens, Sarah Bonato, Patricia Di Ciano","doi":"10.1007/s00213-026-07174-w","DOIUrl":"https://doi.org/10.1007/s00213-026-07174-w","url":null,"abstract":"<p><strong>Rationale: </strong>Cannabis and tobacco are widely used substances with addiction potential, which have opposing effects on cognition and subjective experience and are often co-used in a single occasion.</p><p><strong>Objectives: </strong>The purpose of this systematic review was to synthesize evidence of the acute effects of same-occasion co-use of cannabis and tobacco.</p><p><strong>Methods: </strong>Databases Embase, Medline, CINAHL, PsycINFO, and Web of Science were searched from inception to May 2025. Inclusion criteria were broad. Included studies were peer-reviewed papers, theses, grey literature and abstracts. Designs included randomized controlled trials, laboratory studies, epidemiological studies, qualitative studies, case reports, before-and-after studies, cohort, case-control, cross-sectional, longitudinal, secondary data analysis and naturalistic studies. Papers were screened and selected by two authors and studies were evaluated for quality with the SIGN methodology.</p><p><strong>Results: </strong>In total, 18 studies were included in the present synthesis, and some contained information on multiple outcomes. Five studies examined effects of same-occasion co-use of cannabis and tobacco on cognition; 12 studies evaluated same-occasion co-use on subjective experience; and seven studies evaluated effects on physiological measures. With respect to cognition, three studies found that cannabis and tobacco each attenuated the effects of the other, but the findings were not always consistent. For subjective experience, eight studies reported that the effects of same-occasion co-use of cannabis and tobacco did not differ from the effects of either drug on its own. Two studies of subjective experience found that tobacco dulled the effects of cannabis and two found that tobacco increased the stimulant properties of cannabis.</p><p><strong>Conclusions: </strong>In sum, the evidence for additive effects of cannabis and tobacco is mixed, with some studies reporting that cannabis and tobacco attenuate the effects of the other on cognition. There are inconclusive findings with respect to the combined effects of cannabis and tobacco on subjective effects and physiological outcomes. However, studies are limited and more large-scale studies that investigate the full range of diverse effects of cannabis and tobacco are needed.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114250","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":"Persistent effects of repeated adolescent and adult heroin vapor inhalation in female Wistar rats.","authors":"Arnold Gutierrez, Michael A Taffe","doi":"10.1007/s00213-026-07175-9","DOIUrl":"https://doi.org/10.1007/s00213-026-07175-9","url":null,"abstract":"<p><strong>Rationale: </strong>Drug exposure initiated in adolescence has been associated with more severe mental health outcomes related to substance abuse and anxiety disorders.</p><p><strong>Objectives: </strong>The aim of the present study was to compare the long-term effects of repeated heroin vapor inhalation during adolescence with similar heroin exposure in adulthood.</p><p><strong>Methods: </strong>Groups of female Wistar rats underwent twice daily 30-minute sessions of heroin or propylene glycol (control) vapor inhalation from postnatal days (PND) 36-45 (Adolescent-Exposed) or PND 85-94 (Adult-Exposed). Nociception was assessed after vapor inhalation sessions and forty days later. Anxiety-like behavior was assessed with an elevated plus-maze (EPM) on PND 93/142 and spatial learning was assessed with a Barnes maze from PND 105-116/154-165. Acute effects of naloxone (0.3 mg/kg, i.p.) and heroin (0.5 and 1.0 mg/kg, s.c.) on thermal nociception were determined on PND 140/189 and PND 149/198, respectively.</p><p><strong>Results: </strong>Repeated heroin vapor inhalation produced anti-nociceptive tolerance in both groups, with the Adolescent-Exposed rats exhibiting more complete tolerance. Heroin vapor inhalation produced anxiolytic effects 48 days after repeated exposure. There were no effects of heroin on spatial learning. Naloxone produced acute hyperalgesia in all but the Adolescent-Exposed heroin group, and heroin anti-nociception was blunted in the Adult-Exposed heroin group at the highest heroin dose.</p><p><strong>Conclusions: </strong>Repeated heroin vapor inhalation can produce lasting effects on nociception and anxiety-like behavior that persist for months after the exposure. Importantly, these findings suggest that adolescent exposure to heroin vapor produces specific effects on nociception that are not observed when exposure occurs in adulthood.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114219","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":"Individual differences in behavioral effects of xylazine and opioid-xylazine mixtures in male rats.","authors":"Kristen L Woodhouse, Jun-Xu Li","doi":"10.1007/s00213-025-06988-4","DOIUrl":"10.1007/s00213-025-06988-4","url":null,"abstract":"<p><strong>Rationale: </strong>Recent work in animals suggests xylazine neither enhances the rewarding effects nor intake of fentanyl. Anecdotal evidence from people who use drugs indicates some individuals prefer fentanyl adulterated with xylazine. Systematic examination of pharmacological interactions between xylazine and opioids is needed to understand the disparate findings between preclinical studies and human reports.</p><p><strong>Objectives: </strong>This study examined behavioral interactions between xylazine and opioids in rats to investigate the pharmacology underlying an emerging trend in drug use.</p><p><strong>Methods: </strong>The sedative, hypothermic, subjective, and respiratory effects of xylazine and opioid-xylazine mixtures were examined in male rats. Locomotor activity was measured in an open field, and body temperature changes were measured with a rectal probe. Rats were trained to discriminate 0.04 mg/kg fentanyl, 0.02 mg/kg fentanyl, or 1.5 mg/kg xylazine from saline and were probed with fentanyl, xylazine, or both to observe whether the drug(s) generalized with the training dose. Whole body plethysmography was used to assess the effects of xylazine on respiration.</p><p><strong>Results: </strong>Xylazine depressed locomotor activity and core body temperature, but considerable variability between subjects was observed. In some subjects, xylazine fully substituted for fentanyl, and prolonged the subjective effects of fentanyl. Doses of 1 and 1.78 mg/kg xylazine only partially generalized to the training dose of 1.5 mg/kg xylazine. Xylazine exacerbated the respiratory depressant effects of opioids, and atipamezole reversed the xylazine enhancement of morphine-induced respiratory depression.</p><p><strong>Conclusions: </strong>Individual differences were observed in multiple behavioral measures following xylazine administration and may recapitulate the divisiveness of xylazine reported in people who use drugs.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2351-2367"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725728","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: Chrysin attenuates traumatic brain injury‑induced recognition memory decline, and anxiety/depression‑like behaviors in rats: Insights into underlying mechanisms.","authors":"Masome Rashno, Shahab Ghaderi, Ali Nesari, Layasadat Khorsandi, Yaghoob Farbood, Alireza Sarkaki","doi":"10.1007/s00213-026-07143-3","DOIUrl":"10.1007/s00213-026-07143-3","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2463"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685484","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":"3-Methyladenine administration alleviates cognitive and memory dysfunction in attention-deficit/hyperactivity disorder by modulating autophagy.","authors":"Ge-Ge Lv, Yu-Dong Shan, Jing-Jing Shao, Cao-Yuan Ma, Zhi-Fang Yu, Ji-Zhen Liu, Li-Min Zhang, Wei Zhang","doi":"10.1007/s00213-025-06995-5","DOIUrl":"10.1007/s00213-025-06995-5","url":null,"abstract":"<p><strong>Background: </strong>Attention-deficit/hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder among children, is directly associated with impairments in cognition and memory. In the nervous system, autophagy is essential for the development of neurons, the formation and remodeling of synapses, and the transmission of neurotransmitters. The 3-methyladenine (3-MA), an autophagy inhibitor, mitigates cognitive and memory impairment in neurological disorders. This study aimed to investigate the potential role of 3-MA in ADHD.</p><p><strong>Methods: </strong>An ADHD model was established in offspring mice by intraperitoneal injection of S-ketamine during mid-to-late gestation. Postnatal day 14 offspring received intraperitoneal 3-MA (15 mg/kg/day) or vehicle for 7 consecutive days. To assess behavioral, electrophysiological, and pathological changes in mice, several tests were employed, including the open field test (OFT), novel object recognition (NOR) test, fear conditioning (FC), local field potential recording, western blot, transmission electron microscopy and immunofluorescence assays.</p><p><strong>Results: </strong>Compared to controls, ADHD model mice exhibited: Increased total distance in OFT, Decreased recognition index in NOR, Reduced context- and cue-related freezing time in FC and Attenuated theta oscillation power in the prefrontal cortex. RNA sequencing revealed significant enrichment of the PI3KC3 pathway and autophagy-related genes. ADHD model mice showed upregulated autophagy-related protein expression, elevated LC3II/I ratio, increased autophagosomes, and accumulated abnormal organelles in the mPFC. TH-positive neurities and PSD95-positive puncta were significantly reduced in the mPFC. 3-MA treatment partially reversed these alterations.</p><p><strong>Conclusion: </strong>Cognitive and memory impairments in the mPFC due to ADHD are correlated with autophagy, and these impairments might be alleviated by 3-MA.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2429-2444"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893183","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}