Behavioural PharmacologyPub Date : 2024-12-01Epub Date: 2024-10-08DOI: 10.1097/FBP.0000000000000797
Ismail Akgoz, Huseyin Kara, Ozgen Ozcelik, Levent Donmez, Mehmet Eryilmaz, Gul Ozbey
{"title":"Evaluation of akathisia in patients receiving selective serotonin reuptake inhibitors/serotonin and noradrenaline reuptake inhibitors.","authors":"Ismail Akgoz, Huseyin Kara, Ozgen Ozcelik, Levent Donmez, Mehmet Eryilmaz, Gul Ozbey","doi":"10.1097/FBP.0000000000000797","DOIUrl":"10.1097/FBP.0000000000000797","url":null,"abstract":"<p><p>Akathisia is an underestimated but disturbing extrapyramidal side effect of antidepressants, which could reduce treatment compliance in mood disorders. This study aimed to investigate the frequency and risk factors in patients treated with selective serotonin reuptake inhibitors/serotonin and noradrenaline reuptake inhibitors (SSRI/SNRI). In addition, we assessed the impact of akathisia on the quality of life (QoL). Patients were aged between 18 and 75 years, receiving an SSRI/SNRI for 4-8 weeks, and were diagnosed with anxiety, depression, or obsessive-compulsive disorder. The Barnes Akathisia Rating Scale was used to assess the severity of the akathisia. QoL was evaluated using the Short Form 36 (SF-36) questionnaire. Akathisia was observed in 25% (50/198) of patients. Smokers and younger patients were more frequent among patients with akathisia. Physical functioning, physical role, vitality, and mental health domains of the SF-36 were reduced in the presence of akathisia. In conclusion, our results suggest that akathisia is not a rare side effect of SSRI/SNRI in patients with mood disorders, especially in smokers and younger patients. In addition, akathisia may reduce treatment compliance owing to a reduction in QoL. Further investigations are needed to confirm the risk factors, frequency, and consequences of treatment compliance for SSRI/SNRI-induced akathisia in patients with mood disorders.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"460-463"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380032","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}
Behavioural PharmacologyPub Date : 2024-12-01Epub Date: 2024-10-22DOI: 10.1097/FBP.0000000000000796
Ali Dehghani, Gholam Hossein Meftahi, Hedayat Sahraei
{"title":"The administration of a phentolamine infusion into the basolateral amygdala enhances long-term memory and diminishes anxiety-like behavior in stressed rats.","authors":"Ali Dehghani, Gholam Hossein Meftahi, Hedayat Sahraei","doi":"10.1097/FBP.0000000000000796","DOIUrl":"10.1097/FBP.0000000000000796","url":null,"abstract":"<p><p>The basolateral amygdala (BLA) contains adrenergic receptors, which are known to be involved in stress, anxiety, and memory. The objective of this study was to explore whether inhibition of α-adrenergic receptors (by phentolamine, an α-adrenergic receptor antagonist) in the BLA can reduce foot-shock stress-induced anxiety-like behavior, memory deficits, and long-term potentiation (LTP) deficits within the CA1 region of the rat hippocampus. Forty male Wistar rats were assigned to the intact, control, stress (Str), Phent (phentolamine), and Phent + Str groups. Animals were subjected to six shocks on 4 consecutive days, and phentolamine was injected into BLA 20 min before the animals were placed in the foot-shock stress apparatus. Results from the elevated plus maze test (EPM) revealed a reduction in anxiety-like behaviors (by an increased number of entries into the open arm, percentage of time spent in the open arm, and rearing and freezing) among stressed animals upon receiving injections of phentolamine into the BLA. The open-field test results (increased rearing, grooming, and freezing behaviors) were consistent with the EPM test results. Phentolamine infusion into the BLA enhanced spatial memory, reducing errors in finding the target hole and decreasing latency time in the Barnes maze test for stress and nonstress conditions. Injecting phentolamine into the BLA on both sides effectively prevented LTP impairment in hippocampal CA1 neurons after being subjected to foot-shock stress. It has been suggested that phentolamine in the BLA can effectively improve anxiety-like behaviors and memory deficits induced by foot-shock stress.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"419-431"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457075","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}
Behavioural PharmacologyPub Date : 2024-12-01Epub Date: 2024-10-04DOI: 10.1097/FBP.0000000000000794
Fatemeh Khakpai
{"title":"Norharmane potentiated anxiolytic- and antidepressant-like responses induced by imipramine and citalopram: an isobologram analysis.","authors":"Fatemeh Khakpai","doi":"10.1097/FBP.0000000000000794","DOIUrl":"10.1097/FBP.0000000000000794","url":null,"abstract":"<p><p>β-carboline compounds display a therapeutic property for treating depression and anxiety behaviors. Imipramine and citalopram play an important role in the modulation of anxiety and depression behaviors. We investigated the effects of norharmane, imipramine, and citalopram on anxiety- and depression-like effects and their interactions. Elevated plus maze and forced swimming test were used for the assessment of anxiety- and depression-like behaviors in male mice. The results revealed that intraperitoneal (i.p.) administration of norharmane (10 mg/kg) increased percentage of open arm time (%OAT) in the elevated plus maze test and decreased immobility time in the forced swimming test, proposing anxiolytic- and antidepressant-like effects. Injection of imipramine (5 mg/kg; i.p.) enhanced %OAT and decreased immobility time, suggesting anxiolytic- and antidepressant-like effects. Moreover, norharmane potentiated the anxiolytic- and antidepressant-like responses induced by imipramine by increasing %OAT and decreasing immobility time. The results revealed additive anxiolytic- and antidepressant-like effects between norharmane and imipramine in mice. Alone, the administration of citalopram (5 mg/kg; i.p.) enhanced %OAT and reduced immobility time, causing anxiolytic- and antidepressant-like effects. When citalopram and norharmane were coinjected, norharmane augmented the anxiolytic- and antidepressant-like effects induced by citalopram by increasing %OAT and reducing immobility time. These results indicated additive anxiolytic- and antidepressant-like effects between norharmane and antidepressant drugs such as imipramine and citalopram on the modulation of anxiety and depression processes in mice.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"432-441"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364232","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}
Behavioural PharmacologyPub Date : 2024-12-01Epub Date: 2024-10-15DOI: 10.1097/FBP.0000000000000798
Toni Bird, Madeline M Beasley, Emma M Pilz, Sarah Amantini, Kevin Chavez Lopez, Alan Silberberg, David N Kearns
{"title":"An investigation of economic interactions between social reinforcement and heroin or cocaine in rats.","authors":"Toni Bird, Madeline M Beasley, Emma M Pilz, Sarah Amantini, Kevin Chavez Lopez, Alan Silberberg, David N Kearns","doi":"10.1097/FBP.0000000000000798","DOIUrl":"10.1097/FBP.0000000000000798","url":null,"abstract":"<p><p>The primary goal of the present study was to determine the economic relationship between heroin and social reinforcement in rats: are they substitutes, independents, or complements? In Experiment 1, one group of rats was given a budget of responses that they could allocate between heroin and social reinforcement offered at various combinations of prices. A second group chose between two levers that each resulted in social reinforcement at varying prices when pressed. There was no relationship between the relative allocation of responses between heroin and social reinforcement and changes in their relative prices, indicating that these reinforcers are best viewed as independents. In contrast, when choosing between two sources of social reinforcement, rats increased the allocation of behavior to the cheaper option, confirming that the method used here was sensitive to detecting substitution effects. In Experiment 2, the same method was used to compare one group that chose between heroin and social reinforcement with a second group that chose between cocaine and social reinforcement. The finding that heroin and social reinforcement were independents was replicated. Additionally, there was some evidence that cocaine and social reinforcement were substitutes, at least when the first few minutes of the session were excluded. These results add to our knowledge of how drug and nondrug reinforcers interact in choice situations in rats and may model factors that influence drug use in humans.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"442-452"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Over-the-counter analgesic usage: associations with attentional biases in young women.","authors":"Elise Solbu Roalsø, Sandra Klonteig, Brage Kraft, Siv Skarstein, Eva Hilland, Peyman Mirtaheri, Marianne Aalberg, Rune Jonassen","doi":"10.1097/FBP.0000000000000795","DOIUrl":"10.1097/FBP.0000000000000795","url":null,"abstract":"<p><p>The use of over-the-counter analgesics (OTCA) has been found to alter various aspects of emotional processing and has been linked to increased anxiety and depression symptoms. Attentional bias is an aspect of emotional processing that is closely related to anxiety and depression. Although OTCA and attentional bias have both been linked to anxiety and depression, the potential links between OTCA usage and attentional bias are not yet investigated. The present study aimed to determine whether the frequency of OTCA usage is associated with differences in attentional bias by comparing response-based measures of attentional bias in 62 women aged 19-30 years. The findings showed that the small group reporting high OTCA usage demonstrated more orientation avoidance to fearful stimuli than those reporting no or low usage. Based on these preliminary findings, further research on attentional bias and its relationship to high OTCA usage is recommended.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"453-459"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380033","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}
Neda Alizadeh, Fatemeh Dehbashi, Emad Gholami, Paria Tarahomi, Ali Rashidy-Pour, Abbas Ali Vafaei, Payman Raise-Abdullahi
{"title":"Stress and glucocorticoids impair inhibitory avoidance memory retrieval and extinction in male mice: the ameliorative effect of Ginkgo biloba extract.","authors":"Neda Alizadeh, Fatemeh Dehbashi, Emad Gholami, Paria Tarahomi, Ali Rashidy-Pour, Abbas Ali Vafaei, Payman Raise-Abdullahi","doi":"10.1097/FBP.0000000000000800","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000800","url":null,"abstract":"<p><p>Memory retrieval involves recalling previously consolidated information, while memory extinction refers to the gradual weakening of such memories after recall. Stress and glucocorticoids influence the retrieval and extinction of memory. This study employed a passive avoidance task to examine the impact of acute mild stress and equivalent doses of exogenous corticosterone on fear memory retrieval and extinction in male mice. Subsequently, we investigated the potential therapeutic effects of Ginkgo biloba extract, EGb 761, on memory impairments induced by stress and corticosterone. Corticosterone was administered systemically 30 min before memory reactivation to model glucocorticoid activity during retrieval. Mild acute stress, like the stress levels typically experienced before an exam, was induced through 20-min restraint immediately before reactivation in separate groups. EGb 761 was injected 30 min before corticosterone or stress exposure. Results demonstrated that both corticosterone and acute stress impaired context-specific fear memory retrieval and enhanced subsequent extinction. Pretreatment with EGb 761 inhibited these impairing effects of acute stress and corticosterone on avoidance memory retrieval and extinction. Our findings suggest that the glucocorticoid system and acute stress markedly influence avoidance memory retrieval and extinction. Ginkgo biloba may possess therapeutic and memory-enhancing effects, particularly in stressful situations.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667228","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}
Behavioural PharmacologyPub Date : 2024-10-01Epub Date: 2024-09-11DOI: 10.1097/FBP.0000000000000791
Yanghui Zheng, Guangchao Cheng, Xikai Lin, Jianli Wang
{"title":"Effects of prenatal cocaine exposure on estrous cycle, and behavior and expression of estrogen receptor alpha and oxytocin during estrus and diestrus in mice offspring.","authors":"Yanghui Zheng, Guangchao Cheng, Xikai Lin, Jianli Wang","doi":"10.1097/FBP.0000000000000791","DOIUrl":"10.1097/FBP.0000000000000791","url":null,"abstract":"<p><p>Increasing evidence indicates that prenatal cocaine exposure may result in many developmental and long-lasting neurological and behavioral effects. The behaviors of female animals are strongly associated with the estrous cycle. Estrogen receptors and oxytocin are important neuroendocrine factors that regulate social behavior and are of special relevance to females. However, whether prenatal cocaine exposure induces estrous cycle changes in offspring and whether neurobehavioral changes in estrus and diestrus offspring differ remains unclear. On gestational day 12, mice were administered cocaine once daily for seven consecutive days, then the estrous cycle was examined in adult female offspring, as well as locomotion, anxiety level, and social behaviors, and the expression of estrogen receptor alpha-immunoreactive and oxytocin-immunoreactive neurons were compared between estrus and diestrus offspring. Prenatal cocaine exposure resulted in the shortening of proestrus and estrus in the offspring. During estrus and diestrus, prenatally cocaine-exposed offspring showed increased anxiety levels and changed partial social behaviors; their motility showed no significant differences in estrus, but declined in diestrus. Prenatal cocaine exposure reduced estrogen receptor alpha-immunoreactive expression in the medial preoptic area, ventromedial hypothalamic nucleus, and arcuate nucleus and oxytocin-immunoreactive expression in the paraventricular nucleus in estrus and diestrus offspring. These results suggest that prenatal cocaine exposure induces changes in the offspring's estrous cycle and expression of estrogen receptor alpha and oxytocin in a brain region-specific manner and that prenatal cocaine exposure and the estrous cycle interactively change motility and partial social behavior. Estrogen receptor alpha and oxytocin signaling are likely to play important concerted roles in mediating the effects of prenatal cocaine exposure on the offspring.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"386-398"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124705","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}
Behavioural PharmacologyPub Date : 2024-10-01Epub Date: 2024-07-17DOI: 10.1097/FBP.0000000000000787
David R Maguire
{"title":"Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure.","authors":"David R Maguire","doi":"10.1097/FBP.0000000000000787","DOIUrl":"10.1097/FBP.0000000000000787","url":null,"abstract":"<p><strong>Objectives: </strong>There has been substantial and growing interest in the therapeutic utility of drugs acting at serotonin 2A subtype (5-HT 2A ) receptors, increasing the need for characterization of potential beneficial and adverse effects of such compounds. Although numerous studies have evaluated the possible rewarding and reinforcing effects of 5-HT 2A receptor agonists, there have been relatively few studies on potential aversive effects.</p><p><strong>Methods: </strong>The current study investigated punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in four rhesus monkeys responding under a choice procedure in which responding on one lever delivered a sucrose pellet alone and responding on the other lever delivered a sucrose pellet plus an intravenous infusion of a range of doses of fentanyl (0.1-3.2 µg/kg/infusion), histamine (3.2-100 µg/kg/infusion), or DOM (3.2-100 µg/kg/infusion).</p><p><strong>Results: </strong>When fentanyl was available, responding for a pellet plus an infusion increased dose dependently in all subjects, indicating a positive reinforcing effect of fentanyl. When histamine was available, responding for a pellet plus an infusion decreased in three of four subjects, indicating a punishing effect of histamine. Whether available before or after histamine, DOM did not systematically alter choice across the range of doses tested.</p><p><strong>Conclusion: </strong>These results suggest that the 5-HT 2A receptor agonist DOM has neither positive reinforcing nor punishing effects under a choice procedure that is sensitive to both processes.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"378-385"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behavioural PharmacologyPub Date : 2024-10-01Epub Date: 2024-08-05DOI: 10.1097/FBP.0000000000000789
Yina Sun, Seetha Chebolu, Nissar A Darmani
{"title":"Ultra-low doses of methamphetamine suppress 5-hydroxytryptophan-induced head-twitch response in mice during aging.","authors":"Yina Sun, Seetha Chebolu, Nissar A Darmani","doi":"10.1097/FBP.0000000000000789","DOIUrl":"10.1097/FBP.0000000000000789","url":null,"abstract":"<p><p>The head-twitch response (HTR) in mice is considered a behavioral assay for activation of 5-HT 2A receptors in rodents. It can be evoked by direct-acting 5-HT 2A receptor agonists such as (±)-2,5-dimethoxy-4-iodoamphetamine, 5-hydroxytryptamine precursors [e.g. 5-hydroxytryptophan (5-HTP)], and selective 5-hydroxytryptamine releasers (e.g. d -fenfluramine). The nonselective monoamine releaser methamphetamine by itself does not produce the HTR but can suppress both (±)-2,5-dimethoxy-4-iodoamphetamine- and d -fenfluramine-evoked HTRs across ages via concomitant activation of the inhibitory serotonergic 5-HT 1A or adrenergic α 2 receptors. Currently, we investigated: (1) the ontogenic development of 5-HTP-induced HTR in 20-, 30-, and 60-day-old mice; (2) whether pretreatment with ultra-low doses of methamphetamine (0.1, 0.25, and 0.5 mg/kg, intraperitoneally) can suppress the frequency of 5-HTP-induced HTR at different ages; and (3) whether the inhibitory serotonergic 5-HT 1A or adrenergic α 2 receptors may account for the potential inhibitory effect of methamphetamine on 5-HTP-induced HTR. In the presence of a peripheral decarboxylase inhibitor (carbidopa), 5-HTP produced maximal frequency of HTRs in 20-day-old mice which rapidly subsided during aging. Methamphetamine dose-dependently suppressed 5-HTP-evoked HTR in 20- and 30-day-old mice. The selective 5-HT 1A -receptor antagonist WAY 100635 reversed the inhibitory effect of methamphetamine on 5-HTP-induced HTR in 30-day-old mice, whereas the selective adrenergic α 2 -receptor antagonist RS 79948 failed to reverse methamphetamine's inhibition at any tested age. These findings suggest an ontogenic rationale for methamphetamine's inhibitory 5-HT 1A receptor component of action in its suppressive effect on 5-HTP-induced HTR during development which is not maximally active at a very early age.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"367-377"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103966","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}
Behavioural PharmacologyPub Date : 2024-10-01Epub Date: 2024-09-02DOI: 10.1097/FBP.0000000000000792
Sadaf Fayazzadeh, Sajad Fakhri, Fatemeh Abbaszadeh, Mohammad Hosein Farzaei
{"title":"Role of l -arginine/nitric oxide/cyclic GMP/K ATP channel signaling pathway and opioid receptors in the antinociceptive effect of rutin in mice.","authors":"Sadaf Fayazzadeh, Sajad Fakhri, Fatemeh Abbaszadeh, Mohammad Hosein Farzaei","doi":"10.1097/FBP.0000000000000792","DOIUrl":"10.1097/FBP.0000000000000792","url":null,"abstract":"<p><p>The l -arginine ( l -Arg)/nitric oxide/cyclic GMP/potassium channel (K ATP ) pathway and opioid receptors are known to play critical roles in pain perception and the antinociceptive effects of various compounds. While there is evidence suggesting that the analgesic effects of rutin may involve nitric oxide modulation, the direct link between rutin and the l -Arg/nitric oxide/cyclic GMP/K ATP pathway in the context of pain modulation requires further investigation. The antinociceptive effect of rutin was studied in male NMRI mice using the formalin test. To investigate the role of the l -Arg/nitric oxide/cyclic GMP/K ATP pathway and opioid receptors, the mice were pretreated intraperitoneally with different substances. These substances included l -Arg (a precursor of nitric oxide), S-nitroso- N -acetylpenicillamine (SNAP, a nitric oxide donor), N(gamma)-nitro- l -arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), sildenafil (an inhibitor of phosphodiesterase enzyme), glibenclamide (a K ATP channel blocker), and naloxone (an opioid receptor antagonist). All pretreatments were administered 20 min before the administration of the most effective dose of rutin. Based on our investigation, it was found that rutin exhibited a dose-dependent antinociceptive effect. The administration of SNAP enhanced the analgesic effects of rutin during both the initial and secondary phases. Moreover, L-NAME, naloxone, and glibenclamide reduced the analgesic effects of rutin in both the primary and secondary phases. In conclusion, rutin holds significant value as a flavonoid with analgesic properties, and its analgesic effect is directly mediated through the nitric oxide/cyclic GMP/K ATP channel pathway.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"399-407"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124707","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}