Psychopharmacology最新文献

{"title":"Corticotropin releasing hormone receptor 1 in the medial prefrontal cortex mediates aversion resistant alcohol intake.","authors":"Miranda E Arnold, Cecelia E Harber, Lauren A Beugelsdyk, Ellie B Decker Ramirez, Grace B Phillips, Jesse R Schank","doi":"10.1007/s00213-024-06707-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06707-5","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed.</p><p><strong>Objectives: </strong>We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake.</p><p><strong>Methods: </strong>We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake.</p><p><strong>Results: </strong>After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment.</p><p><strong>Conclusions: </strong>Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522801","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":"A potential role of gut microbiota in stroke: mechanisms, therapeutic strategies and future prospective.","authors":"Manpreet Kaur, Khadga Raj Aran, Raju Paswan","doi":"10.1007/s00213-024-06708-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06708-4","url":null,"abstract":"<p><strong>Rationale: </strong>Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.</p><p><strong>Objective: </strong>The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.</p><p><strong>Results: </strong>Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.</p><p><strong>Conclusion: </strong>In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of voluntary wheel-running exercise on hippocampal neurogenesis and behaviours in response to nicotine cessation in rats.","authors":"Magdalena Zaniewska, Sabina Brygider, Iwona Majcher-Maślanka, Dawid Gawliński, Urszula Głowacka, Sława Glińska, Łucja Balcerzak","doi":"10.1007/s00213-024-06705-7","DOIUrl":"https://doi.org/10.1007/s00213-024-06705-7","url":null,"abstract":"<p><strong>Rationale: </strong>The literature indicates that nicotine exposure or its discontinuation impair adult hippocampal neurogenesis in rats, though the impact of exercise on this process remains unclear. We have previously shown that disturbances in the number of doublecortin (DCX, a marker of immature neurons)-positive (DCX⁺) cells in the dentate gyrus (DG) of the hippocampus during nicotine deprivation may contribute to a depression-like state in rats.</p><p><strong>Objectives: </strong>This study aimed to investigate the effect of running on hippocampal neurogenesis, depression-like symptoms, and drug-seeking behaviour during nicotine deprivation.</p><p><strong>Methods: </strong>The rats were subjected to nicotine (0.03 mg/kg/inf) self-administration via an increasing schedule of reinforcement. After 21 sessions, the animals entered a 14-day abstinence phase during which they were housed in either standard home cages without wheels, cages equipped with running wheels, or cages with locked wheels.</p><p><strong>Results: </strong>Wheel running increased the number of K_i-67⁺ and DCX⁺ cells in the DG of both nicotine-deprived and nicotine-naive rats. Wheel-running exercise evoked an antidepressant effect on abstinence Day 14 but had no effect on nicotine-seeking behaviour on abstinence Day 15 compared to rats with locked-wheel access.</p><p><strong>Conclusions: </strong>In summary, long-term wheel running positively affected the number of immature neurons in the hippocampus, which corresponded with an antidepressant response in nicotine-weaned rats. One possible mechanism underlying the positive effect of running on the affective state during nicotine cessation may be the reduction in deficits in DCX⁺ cells in the hippocampus.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferulic acid ameliorates bisphenol A (BPA)-induced Alzheimer's disease-like pathology through Akt-ERK crosstalk pathway in male rats.","authors":"Mhasen Khalifa, Rabie H Fayed, Yasmine H Ahmed, Mohamed F Abdelhameed, Ahmed F Essa, Heba M A Khalil","doi":"10.1007/s00213-024-06697-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06697-4","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigated the neuroprotective effect of ferulic acid (FA) against bisphenol A (BPA) induced Alzheimer's disease-like pathology in male rats.</p><p><strong>Methods: </strong>Rats were allocated into four groups, control, BPA, BPA + FA, and FA, respectively, for 40 days. Spatial working memory and recognition memory were evaluated. Moreover, the brain levels of oxidative stress biomarkers, proinflammatory cytokines, extracellular signal-regulated kinase (ERK), and phosphorylated serine/threonine protein kinase (p-Akt) were measured. We also determined the brain neuropathological protein levels, including Beta-Amyloid 1-42, total Tau (tTau), and phosphorylated Tau (pTau) proteins. Furthermore, brain levels of Acetylcholinesterase (AChE) and Beta-secretase (BACE) were assessed. Brain histological investigation and immunohistochemistry determination of glial fibrillar acidic protein (GFAP) were also performed. Moreover, docking simulation was adapted to understand the inhibitory role of FA on AChE, BACE-1, and ERK1/2.</p><p><strong>Results: </strong>Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA, which was associated with improved brain redox status. They also exhibited a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels. Moreover, they revealed a decline in beta-amyloid 1-42 and a significant improvement in tTau expression and pTau protein levels in the brain tissue. Further, the brain levels of AChE and BACE were substantially reduced in BPA + FA rats. The neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.</p><p><strong>Conclusion: </strong>FA could be a potent neuroprotectant agent against AD with a possible prospect for its therapeutic capabilities and nutritional supplement value due to its antioxidant and antiapoptotic properties.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506714","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":"Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region.","authors":"Kamlesh Kumar Pandey, Kamakshi Mehta, Balpreet Kaur, Pushpa Dhar","doi":"10.1007/s00213-024-06700-y","DOIUrl":"https://doi.org/10.1007/s00213-024-06700-y","url":null,"abstract":"<p><strong>Rationale: </strong>Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (As₂O₃) in the mouse striatal region.</p><p><strong>Methods: </strong>Healthy adult male mice were chronically administered with varying concentrations of As₂O₃ (2, 4 and 8 mg/kg bw) alone and along with CUR (100 mg/kg bw) orally for 45 days. Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations.</p><p><strong>Results: </strong>Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As₂O₃ compared to controls. Simultaneous treatment of As₂O₃ (2, 4 and 8 mg/kg bw) and curcumin (100 mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As₂O₃ alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As₂O₃ (4 and 8 mg/kg bw). However, these changes were reversed in mice who received As₂O₃ + CUR co-treatment.</p><p><strong>Conclusions: </strong>Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As₂O₃-induced behavioral deficits, as well as biochemical and morphological alterations.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506713","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":"Aerobic exercise prevents and improves cognitive dysfunction caused by morphine withdrawal via regulating endogenous opioid peptides in the brain.","authors":"Shanghua Dai, Yigang Dong, Haifeng Shi, Jiawei Jin, Yixia Gan, Xinyi Li, Yongkang Wu, Fanglin Wang, Xinrui Zhu, Qingmiao Hu, Yi Dong, Yingmei Fu","doi":"10.1007/s00213-024-06698-3","DOIUrl":"https://doi.org/10.1007/s00213-024-06698-3","url":null,"abstract":"<p><strong>Background: </strong>Morphine withdrawal leads to serious cognitive deficits in which dynorphins are directly involved. Recently, exercise has been shown to prevent and improve cognition dysfunction in a variety of ways. Meanwhile, exercise can regulate the endogenous opioid peptides including dynorphins. However, it remains unclear whether exercise influences cognitive dysfunction caused by morphine withdrawal via dynorphins. In the current study, we investigate the physiological mechanism of exercise prevention and improvement aganist cognition dysfunction caused by morphine withdrawal.</p><p><strong>Methods: </strong>Male, adult C57BL/6 mice were randomly divided into 5 groups : Saline control (WT), exercise (EXE), morphine withdrawl (MW), exercise + morphine withdrawl (EMW), morphine withdrawl + exercise (MWE). We established aerobic exercise prevention/improvement models, and conducted behavioral tests including Open field test (OFT), Temporal order memory test (TOM) and Y-maze. Through Western Blotting and immunofluorescence staining, we detected endogenous opioid peptides in hippocampus and mPFC.</p><p><strong>Results: </strong>Compared with MW group, EMW group and MWE group showed the same performance as WT group in TOM and Y-maze, with correct object recognition and memory ability. In Western Blotting and immunofluorescence staining experiments, it indicated that EMW group reduced the expression of PDYN and its fluorescence intensity in hippocampus; MWE group reduced the expression of OPRK1 and its fluorescence intensity in mPFC.</p><p><strong>Conclusion: </strong>Our data suggest that aerobic exercise can both prevent and improve cognitive dysfunction caused by acute morphine withdrawal via respectively down-regulating PDYN in the hippocampus and down-regulating OPRK1 in the mPFC. They may become new targets for drugs development in the future.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473278","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":"Immediate effects of propofol on mood: a randomized comparison of two doses in a cohort with depression.","authors":"Daniel A Feldman, Keith G Jones, Lily C Vonesh, Rebecca Jacobs, Nathan Hoffman, Carter Lybbert, Jason Huang, Kai Kuck, David Odell, Scott C Tadler, Brian J Mickey","doi":"10.1007/s00213-024-06699-2","DOIUrl":"https://doi.org/10.1007/s00213-024-06699-2","url":null,"abstract":"<p><strong>Rationale: </strong>The intravenous anesthetic propofol is known to induce positive mood effects during routine clinical use, suggesting it might be repurposed as an antidepressant, but also raising concerns about abuse potential. How propofol's acute effects vary by dose and with repeated infusions is unknown.</p><p><strong>Objectives: </strong>This exploratory analysis aimed to (1) compare the immediate mood effects of propofol administered at two different doses, (2) describe how those mood effects change with repeated infusions, and (3) evaluate whether acute mood improvement predicts later antidepressant response.</p><p><strong>Methods: </strong>Twenty-four adults with moderate-to-severe treatment-resistant depression were randomized into two dosing groups. Six low- or high-dose propofol infusions were administered under blinded conditions over a two-week period. Self-reported mood states were recorded before and after each infusion using the Positive and Negative Affect Schedule (PANAS-X). Abuse potential was evaluated with the Drug Effects Questionnaire (DEQ-5).</p><p><strong>Results: </strong>At the first infusion, propofol induced acute improvements in PANAS-X Sadness, Fear, Joviality, and Serenity scales (p < 0.002), independent of dose. Over the series of six infusions, acute changes in Sadness, Fear, and Joviality, but not Serenity, diminished with infusion number (p < 0.002). The DEQ-5 \"want more\" rating decreased across infusions (p = 0.002). Changes in PANAS-X scales with the first infusion did not predict later improvement in depression severity (p > 0.05).</p><p><strong>Conclusion: </strong>Cumulative changes in mood states observed with repeated infusions suggest that propofol engages adaptive mechanisms in mood circuitry. Subjective responses with repeated infusions do not indicate increasing potential for abuse in this patient population.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473283","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":"Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.","authors":"Nicole L Zabik, Allesandra Iadipaolo, Craig A Peters, Samantha L Baglot, Matthew N Hill, Christine A Rabinak","doi":"10.1007/s00213-024-06702-w","DOIUrl":"10.1007/s00213-024-06702-w","url":null,"abstract":"<p><strong>Rationale: </strong>Prior work from our lab and others demonstrates that the endocannabinoid system is a promising avenue for improving fear memory deficits in posttraumatic stress disorder (PTSD). Specifically, 7.5 mg of delta-9-tetrahydrocannabinol (THC) decreases fear responding in healthy adults and increases prefrontal cortex activation during extinction learning and fear renewal in adults with PTSD.</p><p><strong>Objectives: </strong>The present study will determine whether there is a dose-dependent effect of THC on short-term (24 h) and long-term (one week) fear learning and memory in adults with PTSD.</p><p><strong>Methods: </strong>Using a randomized, double-blind, placebo-controlled design, N = 36 adults with PTSD completed the study and were randomized to receive placebo (PBO, n = 11), 5 mg of THC (n = 11), or 10 mg of THC (n = 14) prior to fear extinction learning. Participants completed a Pavlovian conditioning paradigm with extinction recall and fear renewal occurring 24 h and one week later, where we measured concurrent functional imaging and behavioral responses.</p><p><strong>Results: </strong>Twenty-four hours after drug administration, individuals with PTSD given 5 mg of THC exhibited greater anterior cingulate cortex and prefrontal cortex activation during early fear renewal. One week later, individuals given 10 mg of THC exhibited greater hippocampus activation during extinction recall and prefrontal cortex activation during fear renewal.</p><p><strong>Conclusions: </strong>These data suggest that dosing and timing are critical for facilitating fear memory processes in PTSD, and that low-dose oral THC prior to extinction learning can affect brain indices of fear learning and memory both acutely and one week after administration.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473280","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":"Assessment of pharmacological effects and abuse potential of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 in mice.","authors":"Kaixi Li, Deli Xu, Yanling Qiao, Lixin Kuai, Xuwen Luo, Bin Di, Peng Xu","doi":"10.1007/s00213-024-06703-9","DOIUrl":"https://doi.org/10.1007/s00213-024-06703-9","url":null,"abstract":"<p><strong>Rationale: </strong>The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.</p><p><strong>Objectives: </strong>We investigated the safety, pharmacological effects, rewarding effects, and cannabinoid withdrawal of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201.</p><p><strong>Methods: </strong>This study evaluated the drug safety and the cannabinoid-specific pharmacological effects of the three substances through acute toxicity experiments (in which the LD₅₀ of each substance was obtained) and tetrad experiments (comprising assessments of hypothermia, analgesia, locomotion inhibition, and catalepsy). Furthermore, the conditioned place preference (CPP) experiments and withdrawal experiments were conducted to evaluate the rewarding effect and cannabinoid withdrawal potential of the substances in question.</p><p><strong>Results: </strong>The results demonstrated that all three drugs exhibited certain acute toxic effects and could potentially induce tetrad effects. The data were analyzed using non-linear regression, and the corresponding ED₅₀ values and 95% confidence intervals (CI) were obtained. The rank order of potency was determined to be CUMYL-PEGACLONE > 5F-EDMB-PICA > NM-2201. In the CPP experiments, it was demonstrated that 5F-EDMB-PICA significantly induced an increase in CPP score at a dose of 0.3 mg/kg, while NM-2201 caused an increase in CPP score and a significant aversion effect at a dose of 2 and 3 mg/kg, respectively. It is noteworthy that all three types of SCs were observed to produce a significant biphasic effect, indicating that CPP scores were biphasic for all compounds. Following the administration of the CB1 receptor antagonist rimonabant, a notable increase in head twitches and paw tremors was observed, indicating that these three SCs induce cannabinoid withdrawal through the mediation of CB1 receptors.</p><p><strong>Conclusions: </strong>The results of this study indicated that these SCs possess cannabinoid-specific pharmacological effects and abuse potential, which provides substantial experimental data to support the future regulation of these substances.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473279","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":"Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear.","authors":"Gabriela V M Oliveira, Paloma M Hernandes, Fábio H Dos Santos, Victor P M N Soares, Luiz Luciano Falconi-Sobrinho, Norberto C Coimbra, Carsten T Wotjak, Rafael Carvalho Almada","doi":"10.1007/s00213-024-06701-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06701-x","url":null,"abstract":"<p><strong>Rationale: </strong>Despite the existing anatomical and physiological evidence pointing to the involvement of orexinergic projections from the lateral hypothalamus (LH) in regulating fear-related responses, little is known regarding the contribution of the orexin system in the prelimbic cortex (PL) on contextual fear.</p><p><strong>Objectives: </strong>We investigated the role of orexin-A (Orx_A) and orexin type 1 receptors (Orx₁R) in the PL during the expression of contextual conditioned fear in mice.</p><p><strong>Methods: </strong>Neural tract tracing of the LH-PL pathway and Orx₁R immunoreactivity in the PL of C57BL/6 male mice were performed. In a pharmacological approach, the animals were treated with either the Orx₁R selective antagonist SB 334,867 (3, 30, and 300 nM/0.1 µL) or Orx_A (28, 70, and 140 pmol/0.1 µL) in the PL before the test session of contextual fear conditioning.</p><p><strong>Results: </strong>Neural tract tracing deposits in the LH showed some perikarya, mainly axons and terminal buttons in the PL, suggesting LH-PL reciprocate pathways. Furthermore, we showed a profuse network comprised of Orx₁R-labeled thin varicose fibers widely distributed in the same field of LH-PL pathways projection. The selective blockade of Orx₁R with SB 334,867 at 30 and 300 nM in the PL caused a decrease in freezing response, whereas the treatment with Orx_A at 140 pmol promoted an increase in freezing response.</p><p><strong>Conclusion: </strong>In summary, these data confirmed an anatomical link between LH and PL, established the presence of Orx₁R in the PL, and a modulatory role of the orexin system in such structure, possibly mainly via Orx₁R, during contextual fear conditioning.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401090","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}