Behavioural Pharmacology最新文献

{"title":"Anxiolytic effects of diazepam in Trinidadian guppies exposed to chemical cues indicating predation risk.","authors":"Adam L Crane, Laurence E A Feyten, Alix J P Brusseau, Félixe Dumaresq Synnott, Indar W Ramnarine, Maud C O Ferrari, Grant E Brown","doi":"10.1097/FBP.0000000000000847","DOIUrl":"10.1097/FBP.0000000000000847","url":null,"abstract":"<p><p>The fear of predation is pervasive among vertebrate prey species, being characterized by neurobiological and behavioral changes induced by risk exposure. To understand the acquisition and attenuation of fearful phenotypes, such as dimensions of posttraumatic stress, researchers often use animal models, with prey fishes recently emerging as a nontraditional but promising model. Much is known about fear acquisition in prey fishes such as the Trinidadian guppy, Poecilia reticulata, which inhabit high and low predation sites. Little is known, however, about whether a guppy model shows fear attenuation via therapeutic treatments, such as commonly prescribed anxiolytic drugs, like benzodiazepines. In this study, we used Trinidadian guppies from wild populations to explore the interactive effects of exposure to the anxiolytic drug, diazepam, and exposure to predation risk in the form of injured conspecific cues (i.e. alarm cues) that reliably indicate a predator attack. In Experiment 1, juvenile guppies from both high- and low-predation populations were given a 10-min exposure to diazepam (160 µg/l), resulting in the loss of fear behavior when simultaneously presented with alarm cues. In Experiment 2, we found that a prior 10-min exposure to diazepam (160 µg/l) for adult guppies significantly reduced their subsequent fear behavior toward a separate exposure to alarm cues, revealing that diazepam was having direct effects on guppy cognition rather than simply inactivating the alarm cues via chemical alteration. These anxiolytic effects thus add to the growing support for the predictive validity of prey fishes as animal models for exploring fear attenuation in humans.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"500-508"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of lithium on behavioral functions in adolescent rats exposed to chronic unpredictable mild stress with respect to brain-derived neurotrophic factor and glycogen synthase kinase-3 beta levels in the prefrontal cortex.","authors":"Maryam Abbasi Mehmandost Sofla, Mahdie Gholami, Salar Vaseghi, Nooshin Barikrow, Batool Ghorbani-Yekta","doi":"10.1097/FBP.0000000000000842","DOIUrl":"10.1097/FBP.0000000000000842","url":null,"abstract":"<p><p>Chronic unpredictable mild stress (CUMS) is widely used as a reliable method to induce depressive states and anhedonia in rodents. Lithium is one of the well-known drugs used for the alleviation of symptoms in different neuropsychiatric disorders such as depression and bipolar disorder. In this research, we evaluated the efficacy of several doses of lithium on behavioral changes induced by CUMS. Also, the expression level of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 beta (GSK-3beta) in the prefrontal cortex was evaluated. CUMS was done using various unpredictable stressors for 14 days. Lithium was injected at the doses of 10, 30, and 50 mg/kg. Locomotor activity, anxiety-like behavior, pain perception, and depressive-like behavior were assessed using the open field test, the novelty-suppressed feeding test, the hot plate test, and the forced swim test, respectively. The results revealed that CUMS decreased locomotor activity, increased anxiety- and depressive-like behaviors, increased pain threshold, decreased climbing, decreased BDNF level, and increased GSK-3beta level in the prefrontal cortex. However, lithium dose-dependently restored all these effects. In control rats, lithium (50 mg/kg) decreased locomotion and GSK-3beta expression levels. In conclusion, the results suggested that deleterious effects of CUMS may be mediated via BDNF and GSK-3beta in the prefrontal cortex, and lithium via suppressing GSK-3beta and upregulating BDNF expression levels in the prefrontal cortex can restore CUMS effects.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"471-483"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haloperidol potentates the antinociceptive effect of buprenorphine and tramadol in rats.","authors":"Rolffy Ortiz-Andrade, Lilian Dolores Chel-Guerrero, Myrna Déciga-Campos","doi":"10.1097/FBP.0000000000000852","DOIUrl":"10.1097/FBP.0000000000000852","url":null,"abstract":"<p><p>This study aimed to evaluate the pharmacological effects of haloperidol on the antinociceptive effects of buprenorphine and tramadol in rats. Dose-response curves were constructed for the individual administration of haloperidol, buprenorphine, and tramadol in rats subjected to the formalin (1%) test. All the compounds demonstrated dose-dependent antinociceptive effects when administered individually. Pharmacological interactions were assessed using an isobolographic method. The doses required to achieve 50% of the maximal antinociceptive effect (ED50) for each drug were combined at a fixed 1 : 1 ratio to establish a combination series of haloperidol + buprenorphine and haloperidol + tramadol. The results showed that buprenorphine achieved a higher maximal antinociceptive effect (98%) compared with tramadol (85%) and haloperidol (84.9%) when administered individually. Isobolographic analysis revealed that the experimental values (Zexp) for haloperidol + buprenorphine (Zadd = 27.6 ± 5.5 vs. Zexp = 5.47 ± 1.2) and haloperidol + tramadol (Zadd = 4987.68 ± 651.5 vs. Zexp = 1678.23 ± 89.8) were significantly lower than the theoretical values (Zadd), indicating synergistic interactions. On the basis of the experimental data, haloperidol potentiated the antinociception in the following order: haloperidol + buprenorphine, followed by haloperidol + tramadol. These findings suggest that such drug combinations could have potential applications in the ongoing research of treatments for chronic pain, depression-related pain, and cancer-associated pain.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"517-525"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention of morphine dependence with a combination of ketotifen and l-carnitine in mice: a new potential therapeutic approach.","authors":"Bohloul Habibi Asl, Solmaz Fallahi, Sanam Bohlouli, Hamid Soltani Zangbar, Tahereh Eteraf-Oskouei","doi":"10.1097/FBP.0000000000000849","DOIUrl":"10.1097/FBP.0000000000000849","url":null,"abstract":"<p><p>Morphine dependence is a complex clinical issue, coinciding with oxidative stress and increased neurotransmitter levels as key factors in this drug's reliance and tolerance. This study examines how l-carnitine, ketotifen, and their combination prevent and treat morphine dependence in mice. Seventy-two male mice (20-25 g) were randomly divided into nine groups. The morphine group received morphine (50 mg/kg/i.p.) for 4 days, while the control group was given saline (10 ml/kg/i.p.). After the morphine administration, three groups received l-carnitine at doses of 25, 50, and 75 mg/kg/i.p., and the following three groups received ketotifen at doses of 4, 8, and 16 mg/kg/i.p. The final group was treated with l-carnitine (25 mg/kg/i.p.) and ketotifen (4 mg/kg/i.p.) after the morphine administration. The morphine dependence was assessed using the jumping and standing on feet indices in the naloxone test. Oxidative stress was evaluated through total antioxidant capacity (TAC) and malondialdehyde (MDA) biomarkers in blood samples. l-carnitine (25, 50, and 75 mg/kg) and ketotifen (4, 8, and 16 mg/kg) reduced the naloxone jumping index. l-carnitine (50 mg/kg) and ketotifen (8 and 16 mg/kg) reduced the standing on feet index. In addition, combining these two medications at modest doses decreased behavioral indices. All three l-carnitine doses and two ketotifen doses lowered MDA and increased TAC. Treating with ketotifen at 4 mg/kg was ineffective; however, when combined with l-carnitine (25 mg/kg), it provided antioxidant benefits. Ketotifen and l-carnitine, by affecting the oxidative stress pathway, reduce the symptoms of morphine dependence and act as potential pharmacological treatments for this condition.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"509-516"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction effect of lithium and crocin on memory performance and behavioral functions in rats exposed to chronic unpredictable mild stress.","authors":"Delaram Khastoo, Fatemeh Jafari, Batool Ghorbani Yekta, Mahsa Ale-Ebrahim, Soheila Fazli-Tabaei, Salar Vaseghi","doi":"10.1097/FBP.0000000000000848","DOIUrl":"10.1097/FBP.0000000000000848","url":null,"abstract":"<p><p>Chronic unpredictable mild stress (CUMS) is an approved method for the induction of depression in rodents. Lithium, as one of the oldest psychiatric drugs, can induce beneficial effects on mood state under stressful conditions. On the other hand, crocin (active component of Saffron) has antioxidant, procognitive, and mood-enhancer effects. In this study, we aimed to investigate the interaction effect of lithium and crocin on mood disturbances and cognitive impairments induced by CUMS. CUMS was performed for 3 weeks. Lithium (100 mg/kg, i.p.), or crocin (30 mg/kg, i.p.), or combination of both was injected during CUMS period (21 injections). Open field test, hot plate, forced swimming test, shuttle box, and Morris water maze were used to evaluate locomotor activity, pain perception, depressive-like behavior, passive avoidance memory, and spatial memory, respectively. The results showed that lithium decreased locomotion and climbing, increased pain threshold and immobility, and impaired passive avoidance and spatial memory in control rats. CUMS also showed all these effects, with more intensity. However, lithium partly reversed the effect of CUMS on locomotion and spatial memory, and completely restored the effect of CUMS on immobility and passive avoidance memory. Also, lithium did not change the effect of CUMS on pain threshold and climbing. Crocin alone, and in combination with lithium significantly reversed all the effects of CUMS. In conclusion, for the first time, the results of the present research showed that the combination of lithium and crocin leads to stronger therapeutic effects on mood disturbances and cognitive impairments induced by chronic stress.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"484-499"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut-brain axis and depression: focus on the amino acid and short-chain fatty acid metabolism.","authors":"Mengjing Chen, Qiuju Lyu, Lina Huang, Yeliang Lou, Lingfeng Wang","doi":"10.1097/FBP.0000000000000851","DOIUrl":"10.1097/FBP.0000000000000851","url":null,"abstract":"<p><p>Depression, a major psychiatric disorder with profound societal impact, remains incompletely understood in its etiology. Identifying novel pathogenic pathways is therefore essential. The gut microbiota ('second brain') critically regulates bidirectional gut-brain axis (GBA) communication with the central nervous system. Dysbiosis correlates strongly with depression, positioning microbiota restoration as a promising therapeutic strategy. Critically, gut microbial metabolic processes - particularly involving amino acids and short-chain fatty acids (SCFAs) - have emerged as key contributors to depression pathogenesis; however, depression-specific alterations in gut microbiota and their metabolic signatures are inadequately characterized, and the molecular mechanisms linking microbial metabolites to depression require further elucidation. This review synthesizes recent advances on GBA-mediated depression pathogenesis, with emphasis on gut dysbiosis-induced disruptions in amino acid and SCFA metabolism, and delineates their mechanistic links to depressive pathophysiology.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"439-453"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valproic acid triggers a sex-independent autism-like deficits, gut-brain axis, and neurodegenerative changes in the autism model of Wistar rats.","authors":"Ashish Jain, Neha Dhir, Amit Raj Sharma, Anupam Raja, Praisy K Prabha, Alka Bhatia, Bikash Medhi, Ajay Prakash","doi":"10.1097/FBP.0000000000000839","DOIUrl":"10.1097/FBP.0000000000000839","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social interaction, communication, restricted interests, and repetitive behaviors. Its higher prevalence in males underscores the importance of understanding potential sex-specific differences. Prenatal exposure to valproic acid (VPA) is a widely used preclinical model to induce ASD-like traits in rodents; however, few studies have systematically compared neurobehavioral outcomes in both sexes. Here, we aimed to investigate sex-specific variations in developmental, behavioral, and physiological parameters in Wistar rat offspring prenatally exposed to VPA. Pregnant rats received a single intraperitoneal injection of VPA (600 mg/kg) or saline on gestational day (GD) 12.5, and offspring were assigned to four groups: control males, control females, VPA males, and females (n = 9 per group). VPA-exposed rats of both sexes exhibited autism-like behaviors, including heightened anxiety, increased exploratory activity, repetitive behaviors, social deficits, spatial and recognition memory impairments, and depressive-like traits. Physiological assessments revealed altered gastrointestinal (GIT) motility, increased brain edema, impaired blood-brain barrier (BBB) function, and neuronal injury with no sex-based difference in estrogen β (ERβ/ESR2) mRNA expression. These findings demonstrate that in utero exposure to VPA induces autism-like behaviors, developmental abnormalities, and neurodegenerative changes in both rat sexes, emphasizing the importance of including females in preclinical ASD research.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"454-470"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Alcea aucheri (Bioss.) Alef extract against scopolamine-induced memory impairment in rats.","authors":"Tajmah Mombeini, Hamid Gholami Pourbadie, Mohammad Kamalinejad, Ahmad Reza Dehpour, Soroush Mazloumi, Reza Hamidian","doi":"10.1097/FBP.0000000000000836","DOIUrl":"10.1097/FBP.0000000000000836","url":null,"abstract":"<p><p>Memory impairment is a core feature of neurodegenerative diseases such as Alzheimer's disease, often modeled using scopolamine-induced cognitive dysfunction in animals. While Alcea aucheri (Boiss.) Alef has demonstrated anxiolytic properties, but its potential impact on cognitive function, particularly memory, remains unexplored. This study investigates the effects of extract of flower of Alcea aucheri (EFA) on cognitive performance in scopolamine-free rats and in a scopolamine-induced memory impairment model. Male Wistar rats were administered EFA [17.5-700 mg/kg, intraperitoneally (i.p.)] across various experimental groups. Cognitive function was assessed using the passive avoidance test for long-term memory and two-trial Y-maze for spatial reference memory. Scopolamine (2 mg/kg, i.p.) was administered to induce memory impairment. The efficacy of EFA in mitigating scopolamine-induced cognitive deficits was evaluated, and memory maintenance was assessed over 6 weeks following treatment. Except for the EFA dose of 700 mg/kg which adversly affected passive avoidance test, its other doses had no significant impact on memory performance in scopolamine-free rats, as observed in both the passive avoidance test and the two-trial Y-maze; however, in rats with scopolamine-induced cognitive deficits, EFA (particularly at 70 mg/kg) significantly improved step-through latency in the passive avoidance test ( P  < 0.001). This suggests a dose-dependent reversal of memory impairment. In addition, EFA demonstrated sustained cognitive enhancement over a 6-week period without affecting body weight. The findings suggest that EFA has a protective effect against scopolamine-induced memory impairment and could serve as a potential therapeutic agent for neurodegenerative conditions associated with cognitive decline. Further research is required to elucidate the underlying mechanisms responsible for these effects.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"387-396"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol improves ovariectomy and chronic restraint stress-induced depression-like behaviors in mice through brain-derived neurotrophic factor associated structural synaptic remodeling.","authors":"Hui Xu, Zhen-Qiang Zhang, Geng Chen, Ming-Jun Ge, Zong-Hao Yu, Jun-Xian Shen, Chuan Pan, Fei Han, Xiu-Ling Zhu, Ya-Ping Lu","doi":"10.1097/FBP.0000000000000845","DOIUrl":"10.1097/FBP.0000000000000845","url":null,"abstract":"<p><p>Previous studies have shown that resveratrol has antidepressant effects in a variety of depression models, but the effect and mechanism of resveratrol on menopausal depression are unclear. In this study, transgenic mice were ovariectomized combined with chronic restraint stress to establish a model of menopausal depression. The antidepressant effect of resveratrol was evaluated by tail suspension test (TST), forced swimming test, sucrose preference test (SPT), and novel inhibition feeding test (NSFT). Using the characteristic expression of yellow fluorescent protein in excitatory neurons of transgenic mice, the effects of resveratrol on the density of dendrites and dendritic spines were evaluated by a three-dimensional imaging technique. Brain-derived neurotrophic factor (BDNF), cofilin1, and p-cofilin1 were quantitatively analyzed by quantitative PCR and immunofluorescence quantification to explore the effects of resveratrol on synaptic plasticity in the hippocampus and medial prefrontal cortex (mPFC) and its mechanism. The results revealed that resveratrol significantly decreased the immobility time in TST, shortened the feeding latency and increased the food intake in NSFT, and enhanced the sucrose consumption in SPT. Consistent with these changes, resveratrol treatment significantly increased the density of p-cofilin1 immunoreactive dendritic spines and the mRNA level of BDNF in these brain regions. The results suggest that resveratrol can improve the synaptic plasticity in the corresponding brain regions by upregulating BDNF levels, enhancing the phosphorylation of cofilin 1, increasing the density of dendrites and dendritic spines in the hippocampus and mPFC, and ultimately improving menopausal depression-like behaviors.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"364-377"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the anti-inflammatory and antinociceptive effects of limonene in two models of carrageenan-induced inflammation and formalin-induced pain: role of l -arginine/nitric oxide/cGMP/K ATP channel signaling pathways, opioidergic, and benzodiazepine receptors.","authors":"Sajad Fakhri, Mostafa Yarmohammadi, Fatemeh Abbaszadeh, Amir Kiani, Mohammad Hosein Farzaei","doi":"10.1097/FBP.0000000000000840","DOIUrl":"10.1097/FBP.0000000000000840","url":null,"abstract":"<p><p>Pain and inflammation are critical and complex biological responses to tissue damage or disease, which significantly impair life quality. The complex pathophysiological mechanisms highlight the necessity for multitarget therapeutic interventions. Limonene, a monoterpene, has shown promising antioxidant and anti-inflammatory properties. This study aimed to elucidate the anti-inflammatory and antinociceptive role of limonene and related mechanisms of action in two animal models. Two models of carrageenan-induced inflammation in rats and formalin-induced pain in mice were employed. In the carrageenan model of inflammation, 30 male Wistar rats were used, including control, diclofenac, and three doses of limonene (5, 10, and 15 mg/kg). The groups followed for 4 h, and paw edema was evaluated using a plethysmometer. In the formalin model of pain, 114 male mice were divided into 19 groups including control, and diclofenac, limonene (5, 10, and 15 mg/kg), l -arginine, N(gamma)-nitro-l-arginine methyl ester (L-NAME), S-nitroso- N -acetylpenicillamine (SNAP), sildenafil, glibenclamide, naloxone, and flumazenil, individually and before the most effective doses of limonene, all intraperitoneal. After the limonene administration, a formalin test was conducted to evaluate pain responses in the mice during both the early neurogenic and late inflammatory phases. The findings indicated that a 10 mg/kg dose of limonene produced the most significant antinociceptive and anti-inflammatory effects. Furthermore, while L-NAME, glibenclamide, naloxone, and flumazenil diminished the antinociceptive properties of limonene, l -arginine, SNAP, and sildenafil increased its effectiveness. This study demonstrated that limonene exhibited antinociceptive and anti-inflammatory properties, mediated through the l -arginine/nitric oxide (NO)/cyclic GMP (cGMP)/ATP-sensitive potassium channel (K ATP ) signaling pathways, opioidergic, and benzodiazepine receptors.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"378-386"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}