Pharmacology Biochemistry and Behavior最新文献

{"title":"Maternal ingestion of cannabidiol (CBD) in mice leads to sex-dependent changes in memory, anxiety, and metabolism in the adult offspring, and causes a decrease in survival to weaning age","authors":"Martina Krakora Compagno ,&nbsp;Claudia Rose Silver ,&nbsp;Alexis Cox-Holmes ,&nbsp;Kari B. Basso ,&nbsp;Caroline Bishop ,&nbsp;Amber Michal Bernstein ,&nbsp;Aidan Carley ,&nbsp;Joshua Cazorla ,&nbsp;Jenna Claydon ,&nbsp;Ashleigh Crane ,&nbsp;Chloe Crespi ,&nbsp;Emma Curley ,&nbsp;Tyla Dolezel ,&nbsp;Ezabelle Franck ,&nbsp;Katie Heiden ,&nbsp;Carley Marie Huffstetler ,&nbsp;Ashley M. Loeven ,&nbsp;Camilla Ann May ,&nbsp;Nicholas Maykut ,&nbsp;Alejandro Narvarez ,&nbsp;Debra Ann Fadool","doi":"10.1016/j.pbb.2024.173902","DOIUrl":"10.1016/j.pbb.2024.173902","url":null,"abstract":"<div><h3>Rationale</h3><div>The consequences of perinatal cannabidiol (CBD) exposure are severely understudied, but are important, given its widespread use and believed safety as a natural supplement.</div></div><div><h3>Objective</h3><div>The objective of this study was to test the health, metabolic, and behavioral consequences of perinatal CBD exposure on dams and their offspring raised to adult.</div></div><div><h3>Methods</h3><div>Primiparous female C57BL/6J mice were orally administered 100 mg/kg CBD in strawberry jam to expose offspring during gestation, lactation, or both using a cross-fostering design. Adult offspring were metabolically profiled using indirect calorimetry and intraperitoneal glucose tolerance testing. Adults were behaviorally phenotyped, video recorded, and mouse position tracked using DeepLabCut.</div></div><div><h3>Results</h3><div>CBD was detected in maternal plasma using LC-MS 10-min post consumption (34.2 ± 1.7 ng/μl) and peaked within 30 min (371.0 ± 34.0 ng/μl). Fetal exposure to CBD significantly decreased survival of the pups, and decreased male postnatal development, but did not alter litter size, maternal body weight or pup birth weight. We observed many sex-dependent effects of perinatal CBD exposure. Exposure to CBD during gestation and lactation increased meal size, caloric intake, and respiratory exchange ratio for adult male offspring, while exposure during lactation decreased fasting glucose, but had no effect on clearance. Adult female offspring exposed to CBD during lactation showed increased drink size. Perinatal CBD exposure increased obsessive compulsive- and decreased anxiety-like behaviors (marble burying, light-dark box, elevated-plus maze) in female mice, decreased long-term object memory in male mice, and had no effect on attention tasks for either sex.</div></div><div><h3>Conclusions</h3><div>We conclude that orally-administered CBD during pregnancy affects behavior and metabolism in a sex-dependent manner, and mice are differentially sensitive to exposure during gestation vs. lactation, or both. Because long-term changes are observed following perinatal exposure to the drug, and exposure significantly decreases survival to weaning, more research during development is warranted.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173902"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors as anti-alzheimer agents via in-silico-based drug design, virtual screening, molecular docking, molecular dynamics simulation, DFT, and non-clinical studies","authors":"Smita Jain ,&nbsp;Ritu Singh ,&nbsp;Tripti Paliwal ,&nbsp;Kanika Verma ,&nbsp;Jaya Dwivedi ,&nbsp;Sarvesh Paliwal ,&nbsp;Swapnil Sharma","doi":"10.1016/j.pbb.2024.173943","DOIUrl":"10.1016/j.pbb.2024.173943","url":null,"abstract":"<div><h3>Aim</h3><div>To identify some novel fatty acid hydrolase (FAAH) inhibitors that may contribute to the treatment of Alzheimer's disease (AD).</div></div><div><h3>Methods</h3><div>In-silico pharmacophore modelling including ligand-based pharmacophore modelling, virtual screening, molecular docking, molecular dynamics modelling, density functional theory and in-silico pharmacokinetics and toxicological studies were employed for the retrieving of novel FAAH inhibitors. Further, these compounds were evaluated for FAAH inhibitory activity using an in vitro enzymatic assay, and later, an in vivo streptozotocin (STZ)-induced AD model was examined in mice.</div></div><div><h3>Results</h3><div>Using an in-silico pharmacophore modelling process with molecular docking, molecular dynamic modelling, density functional theory and in-silico pharmacokinetics and toxicological analysis, three compounds (NCI1697, NCI1001and NCI1041) were retrieved. The in vitro FAAH activity assay kit (Fluorometric) was employed to examine the FAAH inhibitory activity of identified compounds. Further, in in-vivo studies, treatment with these compounds at 2.5 and 5 mg/kg doses orally for 10 days restored the STZ-induced memory deficits in mice, as evident in the radial arm and Morris's water maze assays. Also, these compounds ameliorated oxidative stress profiles and neuroinflammatory biomarkers in mice. Interestingly, STZ-induced disturbance in gene expressions related to AD pathophysiology including endocannabinoid signalling neuroinflammation and neuroimmune signalling were also restored after the treatment. Histopathological findings also confirmed the improvement in the organization of cells and reduction in vacuolation in mice hippocampal tissue in treated mice.</div></div><div><h3>Conclusion</h3><div>The in-silico, in vitro and in-vivo findings collectively indicated that these compounds have impressive FAAH inhibitory activity and may be developed as therapeutic agents in the management of AD.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173943"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine impairs the performance of male mice in novel recognition object test and reduces the immunoreactivity of GAD67 in the hippocampus: Role of pioglitazone","authors":"Talita Rodrigues ,&nbsp;Getulio Nicola Bressan ,&nbsp;Patrícia Zorzi Juliani ,&nbsp;Maria Eduarda Brandli da Silva ,&nbsp;Roselei Fachinetto","doi":"10.1016/j.pbb.2024.173950","DOIUrl":"10.1016/j.pbb.2024.173950","url":null,"abstract":"<div><div>Schizophrenia is a mental disorder characterized by positive, negative, and cognitive symptoms which is treated with antipsychotics. However, these drugs present several side effects and, some schizophrenia symptoms, like cognitive, are difficult to treat. The peroxisome proliferator-activated receptors-gamma (PPAR-γ) are expressed in dopaminergic neurons of the midbrain participating in the modulation of dopamine-mediated behavior . We investigated the effects of pioglitazone, an agonist of PPAR-γ, on the behavioral alterations induced by ketamine and, whether alterations in monoamine oxidase (MAO) activity, glutamic acid decarboxylase (GAD₆₇), PPAR-γ or tyrosine hydroxylase (TH) immunoreactivity in brain tissues are involved in these effects. Male mice received ketamine (30 mg/kg), intraperitoneally, for 14 consecutive days, and pioglitazone (3 or 9 mg/kg), by gavage (day 8 up to day 14). Ketamine decreased nail-biting increasing the time exploring the center of the open field on day 8 and the number of rearing evaluated 30 min after its administration on day 14. Furthermore, ketamine decreased the percentage of investigation in the NOR test and the immunoreactivity of GAD₆₇ in the hippocampus. No significant changes were found in other behavioral and biochemical tests. Pioglitazone attenuated the effects of ketamine on rearing and GAD₆₇ immunoreactivity in the hippocampus, recovering the ketamine effects on NOR test. At a dose of 9 mg/kg, pioglitazone alone reduced the immunoreactivity of GAD₆₇ in the hippocampus. Pioglitazone at both doses recovered the cognitive symptoms induced by ketamine an effect that seems to involve the modulation of GAD₆₇ immunoreactivity in the hippocampus. In conclusion, pioglitazone improved the effects of ketamine on the NOR test which was, at least in part, associated with the modulation of GAD₆₇ immunoreactivity in the hippocampus suggesting its beneficial role in cognitive symptoms.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173950"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibitory effect of nicotine on Lumbriculus variegatus stereotypical movements and locomotor activity.","authors":"Nia A Davies, Julanta J Carriere, Aneesha Gopal, Annie Rajan, Melisa J Wallace, Aidan Seeley","doi":"10.1016/j.pbb.2024.173953","DOIUrl":"10.1016/j.pbb.2024.173953","url":null,"abstract":"<p><p>Nicotine has been shown to induce profound physiological and behavioural responses in invertebrate model organisms such as Caenorhabditis elegans and Drosophila melanogaster. Lumbriculus variegatus is an aquatic oligochaete worm which we have previously demonstrated has application within pharmacological research. Herein, we demonstrate the presence of endogenous acetylcholine and cholinesterase activity within L. variegatus and show the time-dependent effects on the sensitivity of L. variegatus to nicotine. We describe the effects of a broad range of concentrations of nicotine (1 μM - 1 mM) on L. variegatus response to tactile stimulation and locomotor activity following acute (10-min) and chronic (24-h) exposure. Here, we show that 10 min of exposure to ≥0.1 mM nicotine reversibly reduces the ability of tactile stimulation to elicit stereotypical movements of body reversal and helical swimming, and locomotor activity in L. variegatus. We also demonstrate that exposure to ≥0.1 mM nicotine for 24 h was toxic to L. variegatus. Chronic low-dose nicotine ≥25 μM similarly inhibits L. variegatus behaviours with 50 μM causing irreversible inhibition of movement. Thus, L. variegatus presents a model for studying the effects of nicotine and further demonstrates the application of the in vivo model L. variegatus for behavioural pharmacology research.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173953"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juvenile chronic social defeat stress reduces prosocial behavior in adult male mice.","authors":"Zihan Zhao, Mingxu Zhang, Qiqi Tang, Minghao Lu, Xiangyu An, Yajie Cui, Mingyang Zhao, Ningyuan Qian, Juan Shao, Haishui Shi, Xiaojuan Qie, Li Song","doi":"10.1016/j.pbb.2024.173941","DOIUrl":"10.1016/j.pbb.2024.173941","url":null,"abstract":"<p><p>Exposure to stress in early life can have a significant impact on individuals. However, the effects of early-life stress (ELS) on prosocial behavior remain unclear, as do the underlying mechanisms. In this study, ICR juvenile mice were subjected to juvenile chronic social defeat stress (jCSDS) between postnatal days 32 and 41, during which body weight changes were continuously monitored. The behaviors of adult mice were evaluated using the open field test (OFT), the social interaction test (SIT), and the prosocial choice task (PCT). ELISA was used to quantify serum levels of oxytocin, serotonin, and dopamine. The density of dendritic spines in the basolateral amygdala was evaluated by Golgi staining. Behavioral test results showed that jCSDS induced anxiety-like behavior and decreased prosocial selection tendency in mice. Additionally, exposure to jCSDS increased the serum levels of oxytocin, decreased those of serotonin, and increased the density of dendritic spines in the basolateral amygdala. Correlation analysis indicated that prosocial behavior was negatively correlated with serum oxytocin levels and dendritic spine density in the basolateral amygdala. These results suggested that jCSDS reduced prosocial behavior, possibly due to changes in serum oxytocin contents and adaptive changes in amygdaloid neurons.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173941"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeine intake during gestation and lactation causes long-term behavioral impairments in heterogenic mice offspring in a sex-dependent manner.","authors":"Bruna da Silva Oliveira, Thaís de Mérici Domingues Paula, Lucas Carvalho Cardoso, João Vitor Lopes Ferreira, Caroline Amaral Machado, Heliana de Barros Fernandes, Brener Cunha Carvalho, Ingrid Dos Santos Freitas, Lorena Taveira Nogueira, Antônio Lúcio Teixeira, Eliana Cristina de Brito Toscano, Aline Silva de Miranda, Fernanda Radicchi Campos Lobato de Almeida","doi":"10.1016/j.pbb.2024.173949","DOIUrl":"10.1016/j.pbb.2024.173949","url":null,"abstract":"<p><p>Growing evidence has indicated a potential association between maternal consumption of caffeine and impaired cognition and behavior in rodent offspring. However, potential sex differences, as well as caffeine-related effects in subsequent generations are still poorly investigated. We aimed to investigate the impact of pre-and/or neonatal exposition to caffeine on the neurodevelopment of male and female mice offspring. Adult female Swiss mice were randomly divided into four experimental groups, which received, via gavage, water or caffeine (120 mg/day). Control/control (CC) received water during pregnancy and lactation; treated/control (TC): received caffeine during pregnancy and water during lactation; control/treated (CT): received water during pregnancy and caffeine during lactation; treated/treated (TT): received caffeine during pregnancy and lactation. Dams were euthanized at gestational day 17.5 and fetal brains were collected. Adult mice of F1 and F2 generations were submitted to behavioral analysis and their pre-frontal cortex and hippocampi were dissected to measure the levels of BDNF and CX3CL1. Caffeine induced reduction of CX3CL1 levels in female fetuses compared with controls. Maternal intake of caffeine was associated with anxiety- and compulsive-like behavior in both F1 and F2 female mice offspring. Interestingly, only F2 female mice exhibited caffeine-induced impairment of work memory. Hippocampal levels of CX3CL1 and BDNF were decreased in female F1TT and F2TT groups; while among males exposed to caffeine, only F1 offspring had reduced hippocampal CX3CL1 levels. Our results suggest that both pre- and neonatal exposition to caffeine lead to long-term behavioral and neurochemical impairments in a sex-dependent manner, adversely affecting the subsequent female generation.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173949"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice","authors":"Johanna E.L. Möller ,&nbsp;Franziska W. Schmitt ,&nbsp;Daniel Günther ,&nbsp;Alicia Stöver ,&nbsp;Yvonne Bouter","doi":"10.1016/j.pbb.2024.173944","DOIUrl":"10.1016/j.pbb.2024.173944","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is characterized by cognitive decline, with pathological features including amyloid β (Aβ) plaques and inflammation. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease-modifying and easily accessible therapies. The endocannabinoid system presents a promising target for AD treatment, as it regulates various processes implicated in AD pathogenesis.</div></div><div><h3>Aims</h3><div>This study assesses the effects of the synthetic cannabinoid WIN 55,212-2 on AD pathology and behavior deficits in aged 5XFAD mice, a well-established AD model.</div></div><div><h3>Methods</h3><div>Male 9-month-old 5XFAD mice received either 0.2 mg/kg WIN 55,212-2 or a vehicle solution for 42 days. Memory, anxiety, and motor tests were conducted at 10 months to identify potential changes in behavior and cognition following WIN 55,212-2 treatment. Additionally, the effects of prolonged WIN 55,212-2 treatment on Aβ pathology and neuroinflammation in the brain were quantified immunohistochemically.</div></div><div><h3>Results</h3><div>Therapeutic WIN 55,212-2 treatment improved the motor performance of 5XFAD mice on the rotarod and rescued memory deficits in the water maze. However, WIN 55,212-2 treatment did not significantly affect anxiety-like behavior in 5XFAD mice. Additionally, prolonged treatment with WIN 55,212-2 reduced Aβ plaque pathology and astrogliosis in the cortex and hippocampus.</div></div><div><h3>Conclusions</h3><div>This study highlights the therapeutic potential of WIN 55,212-2 in AD by ameliorating cognitive and motor deficits and reducing neuropathology. These findings support a cannabinoid-based therapy as a promising strategy for AD treatment, with WIN 55,212-2 emerging as a potential candidate.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173944"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the alcohol-sleep-hangover relationship in college students using a daily diary approach","authors":"Neel Muzumdar ,&nbsp;Kristina M. Jackson ,&nbsp;Jennifer F. Buckman ,&nbsp;Andrea M. Spaeth ,&nbsp;Alexander W. Sokolovsky ,&nbsp;Anthony P. Pawlak ,&nbsp;Helene R. White","doi":"10.1016/j.pbb.2024.173910","DOIUrl":"10.1016/j.pbb.2024.173910","url":null,"abstract":"<div><div>This daily diary study expands knowledge of the pharmacological alcohol-sleep relationship using a multilevel modeling approach. The interplay between alcohol and sleep on hangover susceptibility is also explored. College students (<em>n</em> = 337; 52 % female) provided 2976 days of self-reported alcohol use. We regressed sleep duration onto accumulated sleep debt, prior night sleep duration, and estimated blood alcohol concentration (eBAC) at bedtime; linear mixed models disaggregated day and person-level effects. Binomial models, assessing days after drinking when eBAC = 0 % versus when eBAC&gt;0 % at waketime, regressed hangover susceptibility onto the same predictors plus sleep duration. More accumulated sleep debt predicted slightly longer same-night sleep. Greater than average bedtime intoxication predicted longer than average same-night sleep when drinking ceased early, but later drinking attenuated the relationship. People who typically stopped drinking later in the night reported typically shorter sleep durations on drinking nights. When waketime eBAC = 0 %, higher eBAC at bedtime and drinking later on a given night predicted greater next-day hangover susceptibility. Typical bedtime eBAC and typically later drinking predicted typically greater hangover susceptibility. When waketime eBAC&gt;0 %, longer sleep duration predicted more likely hangovers. Bedtime eBAC and sleep debt interacted, such that more sleep debt attenuated the positive association between intoxication and next-day hangover susceptibility. Late-night drinking appeared to reduce sleep duration and increase hangover susceptibility. Accumulated sleep debt complicated the alcohol-sleep-hangover relationship. External factors influencing sleep behaviors were not assessed, but the results highlight the need to deconstruct sleep into acute and chronic processes. Future studies should better subdivide physiological processes related to hangovers.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173910"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome depletion by broad-spectrum antibiotics does not influence demyelination and remyelination in cuprizone-treated mice","authors":"Rumi Murayama ,&nbsp;Guilin Liu ,&nbsp;Ming-ming Zhao ,&nbsp;Dan Xu ,&nbsp;Ting-ting Zhu ,&nbsp;Yi Cai ,&nbsp;Yong Yue ,&nbsp;Hiroyuki Nakamura ,&nbsp;Kenji Hashimoto","doi":"10.1016/j.pbb.2024.173946","DOIUrl":"10.1016/j.pbb.2024.173946","url":null,"abstract":"<div><div>Demyelination in the central nervous system (CNS) is a feature of various psychiatric and neurological disorders. Emerging evidence suggests that the gut-brain axis may play a crucial role in CNS demyelination. The cuprizone (CPZ) model, which involves the administration of CPZ-containing food pellets, is commonly used to study the effects of different compounds on CNS demyelination and subsequent remyelination. This study aimed to evaluate the impact of microbiome depletion, induced by an antibiotic cocktail (ABX), on demyelination in CPZ-treated mice and the subsequent remyelination following CPZ withdrawal. Our findings indicate that a chronic 4-week oral ABX regimen, administered both during and after a 6-week CPZ exposure, does not affect demyelination or remyelination in the brains of CPZ-treated mice. Specifically, ABX treatment for 2 weeks before and 2 weeks after CPZ exposure, in the final 4 weeks before sacrifice, and for 4 weeks post-CPZ withdrawal, did not significantly alter these processes compared to control mice receiving water instead of ABX. These results indicate that despite effective microbiome depletion, a 4-week oral ABX regimen does not influence demyelination or remyelination in the CPZ model. Thus, it is unlikely that gut microbiota depletion by ABX plays a significant role in these processes. However, further research is needed to fully understand the role of the host microbiome on CPZ-induced demyelination.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173946"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today.","authors":"Daniel P Radin, Arnold Lippa, Sabhya Rana, David D Fuller, Jodi L Smith, Rok Cerne, Jeffrey M Witkin","doi":"10.1016/j.pbb.2025.173967","DOIUrl":"https://doi.org/10.1016/j.pbb.2025.173967","url":null,"abstract":"<p><p>α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors (AMPA receptors or AMPARs) are involved in fast excitatory neurotransmission and as such control multiple important physiological processes. AMPARs also are involved in the dynamics of synaptic plasticity in the nervous system where they impact neuroplastic responses such as long-term facilitation and long-term potentiation that regulate biological functions ranging from breathing to cognition. AMPARs also regulate neurotrophic factors that are strategically involved in neural plastic changes in the nervous system. As with other major ionotropic receptors, modulation of AMPARs can have prominent effects on biological systems that can include marked tolerability issues. AMPAR potentiators (AMPAkines) are positive allosteric modulators of AMPARs which have clear therapeutic potential. Medicinal chemistry combined with new pharmacological findings have defined AMPAkines with favorable oral bioavailability and pharmacological safety parameters that enable clinical advancement of their therapeutic utility. AMPAkines are being investigated in patients with diverse neurological and psychiatric disorders including spinal cord injury (breathing and bladder function), cognition, attention-deficit-hyperactivity disorder, and major depressive disorder. The present discussion of this class of compounds focuses on their general value as therapeutics through their impact on synaptic plasticity.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173967"},"PeriodicalIF":3.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}