Behavioural PharmacologyPub Date : 2025-09-01Epub Date: 2025-07-08DOI: 10.1097/FBP.0000000000000843
Meghan Hibicke, Charles D Nichols
{"title":"Using UAS-Gal4 designer receptors exclusively activated by designer drugs to elucidate nondopaminergic modulation of methamphetamine-induced locomotion in Drosophila.","authors":"Meghan Hibicke, Charles D Nichols","doi":"10.1097/FBP.0000000000000843","DOIUrl":"10.1097/FBP.0000000000000843","url":null,"abstract":"<p><p>Methamphetamine (METH) use disorder is a serious public health problem with no Food and Drug Administration-approved therapeutic drugs to aid recovery. METH's primary mechanism of action increases dopaminergic neurotransmission in brain regions implicated in reward. However, the serotonergic system is also involved in reward processing and dopamine modulation, thus drugs affecting the serotonin system may have therapeutic potential for treating METH use disorder. To use male and female UAS-Gal4 flies expressing designer receptors exclusively activated by designer drugs to investigate the contributions of nondopaminergic neurons on locomotor response to METH over multiple days, as measured by the Drosophila activity monitoring system. While METH increased locomotor activity in most flies, sex and strain also contribute to METH response, with males of most fly strains displaying significantly greater METH-induced locomotor activity than females. We found METH-induced locomotor activity to be highly modulated by serotonergic signaling and circadian regulators. The mushroom body, serotonin availability, 5-HT 1A neurons, 5-HT 7 neurons, drosophila insulin-like protein neurons, and pigment dispersing factor neurons modulate locomotor activity independent of METH response. The mushroom body, 5-HT 7 neurons, and drosophila insulin-like protein neurons also modulate METH response. While all the neuron types investigated were shown to modulate locomotor activity in some way, 5-HT 7 neurons appear to mediate METH-induced locomotor response most directly.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"415-428"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574776","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 : 2025-09-01Epub Date: 2025-07-15DOI: 10.1097/FBP.0000000000000844
Tamires Martins, Ana B Ramos-Hryb, Marcus Antonio B da Silva, Camila Sant' Helena do Prado, Fabíola B Eckert, Fabiani F Triches, Johnny E da Costa, Juliana A Bolzan, Sarah K McCann, Cilene Lino de Oliveira
{"title":"Antidepressant effect or bias? Systematic review and meta-analysis of studies using the forced swimming test.","authors":"Tamires Martins, Ana B Ramos-Hryb, Marcus Antonio B da Silva, Camila Sant' Helena do Prado, Fabíola B Eckert, Fabiani F Triches, Johnny E da Costa, Juliana A Bolzan, Sarah K McCann, Cilene Lino de Oliveira","doi":"10.1097/FBP.0000000000000844","DOIUrl":"10.1097/FBP.0000000000000844","url":null,"abstract":"<p><p>The forced swim test (FST) assesses antidepressant activity in rodents by measuring suppression of immobility. This study reviewed the literature to evaluate how experimental conditions, study quality, and bias influence antidepressant efficacy in the FST (PROSPERO: CRD42020200604). Systematic searches in Embase and MEDLINE (PubMed) identified 8247 relevant records. After being screened by two independent reviewers, 2588 records were included in the library. A random sample ( k = 200) yielded 561 studies for meta-analysis. One reviewer extracted data, double-checked by a second; discrepancies were resolved by a third. Meta-analyses were conducted using a random-effects model (metafor R package) to estimate combined effect size (CES), 95% confidence intervals (CI), heterogeneity, and publication bias. Risk of bias was assessed via SYRCLE's tool and the CAMARADES checklist. Despite high inconsistency ( I ² = 81.5%), the global CES was large and significant [Hedges' g = 1.66, 95% CI (1.53; 1.79), k = 561, power > 80%], consistent across most subgroups. Small study effects and publication bias inflated CES estimates, especially in mice, while results in rats were more variable. Nonetheless, antidepressants consistently reduced immobility in mice across diverse conditions. In rats, findings were less consistent, though the most robust data showed a significant, dose-dependent antidepressant-like effect of imipramine in both species. However, publication bias and incomplete reporting compromise the accuracy of CES estimates and raise concerns about the validity of the FST literature. These findings highlight the need for more transparent reporting practices in FST-based antidepressant research.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"347-363"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759036","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 : 2025-09-01Epub Date: 2025-07-07DOI: 10.1097/FBP.0000000000000841
Kaixi Li, Nan Li, Yuanyuan Chen, Xiangyu Li, Yanling Qiao, Dan Wang, Bin Di, Peng Xu
{"title":"Effects of three tryptamines: alpha-methyltryptamine, 5-methoxy-alpha-methyltryptamine, and 5-methoxy- N , N -diisopropyltryptamine on acute toxicity, locomotor activity, and hallucinogenic behavior in mice.","authors":"Kaixi Li, Nan Li, Yuanyuan Chen, Xiangyu Li, Yanling Qiao, Dan Wang, Bin Di, Peng Xu","doi":"10.1097/FBP.0000000000000841","DOIUrl":"10.1097/FBP.0000000000000841","url":null,"abstract":"<p><p>Alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), and 5-methoxy- N , N -diisopropyltryptamine (5-MeO-DiPT) are synthetic tryptamines with hallucinogenic-like properties that are widely abused worldwide. There, however, has been a paucity of research and a lack of available data on their pharmacological properties. The objective of this study was to investigate the safety of AMT and 5-MeO-DiPT and to compare the effects of AMT, 5-MeO-AMT, and 5-MeO-DiPT under identical conditions in terms of locomotor performance and hallucinogenic-like behavior, and the role of 5-hydroxytryptamine-2A receptor antagonists (M100907) on hallucinogenic-like behavior. The results showed that both AMT and 5-MeO-DiPT exhibited some acute toxic effects. AMT, 5-MeO-AMT, and 5-MeO-DiPT inhibited locomotor activity and induced head-twitch response (HTR) in mice. Pretreatment with M100907 (0.01 mg/kg) blocked AMT, 5-MeO-AMT, and 5-MeO-DiPT induced HTR in mice. The findings of this study demonstrated that the three tryptamines are toxic, inhibit locomotor activity, and have hallucinogenic effects. These results provide experimental data that can provide fundamental support for future control strategies and in-depth mechanistic studies of these substances.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"429-437"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574774","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 : 2025-09-01Epub Date: 2025-07-01DOI: 10.1097/FBP.0000000000000838
Yami Bright, Helene I V Amatdjais-Groenen, Michel M M Verheij, Petra H H van den Broek, Marcia Spoelder, Dorien Maas, Rick Greupink, Gerard J M Martens, Judith R Homberg
{"title":"Procognitive effects of methyl 2-amino-3-methoxybenzoate (or daopine) may involve the dorsal striatal anthranilic acid pathway and mutimetabolite-multitarget pharmacology.","authors":"Yami Bright, Helene I V Amatdjais-Groenen, Michel M M Verheij, Petra H H van den Broek, Marcia Spoelder, Dorien Maas, Rick Greupink, Gerard J M Martens, Judith R Homberg","doi":"10.1097/FBP.0000000000000838","DOIUrl":"10.1097/FBP.0000000000000838","url":null,"abstract":"<p><p>Multifunctional drug treatment is currently the most promising approach in neuropsychopharmacology to overcome complex disorders, such as schizophrenia. We previously showed that the natural protoalkaloid, methyl 2-amino-3-methoxybenzoate [or daopine (DAO)] has procognitive effects in animal models of schizophrenia. Because DAO is a metabolite of the anthranilic acid biosynthesis pathway in Nigella damascena plant seeds, we sought to find out if DAO exerts its procognitive effects via the 'anthranilic acid-brain-pathway-twin' and mutimetabolite-multitarget pharmacology. We explored the procognitive effects of DAO using the operant set shift task in a rat model of attentional flexibility deficits induced by L-kynurenine, the precursor of both kynurenic acid and anthranilic acid. HPLC and liquid chromatography-mass spectrometry was used to identify brain and plasma DAO metabolites and the effects of DAO on dorsal striatal anthranilic acid. DAO attenuated kynurenine-induced cognitive deficits. We identified for the first time the brain (DAO-1 and DAO-3) and plasma (DAO-1 and DAO-2) metabolites of DAO, which remarkably are all methylated derivatives of 3-hydroxyanthranilic acid (3-OHAA), an endogenous brain astrocytic metabolite of anthranilic acid playing a crucial role in cognition. In vitro , DAO-2 and DAO-3 significantly reduced oxidative activity, lipid peroxidation, inflammation, and amyloid β-42-aggregation, all of which represent processes that play an important protective role against cognitive dysfunction. The results strengthen our hypothesis that administering small molecules structurally related to anthranilic acid/3-OHAA, such as DAO, may provide a multitarget strategy for the prevention and treatment of cognitive deficits in schizophrenia, and more broadly, in other cognitive disorders, such as Alzheimer's disease.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"397-414"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537957","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}
Ashish Jain, Neha Dhir, Amit Raj Sharma, Anupam Raja, Praisy K Prabha, Alka Bhatia, Bikash Medhi, Ajay Prakash
{"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":"https://doi.org/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":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991398","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}
Mengjing Chen, Qiuju Lyu, Lina Huang, Yeliang Lou, Lingfeng Wang
{"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":"https://doi.org/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":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991408","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":"https://doi.org/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":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991413","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":"https://doi.org/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":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991476","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":"Synbiotic diet produces antidepressant-like effects but alters ketamine activity in an avian model of treatment-resistant depression.","authors":"Stephen W White, Tara D Clover, Kenneth J Sufka","doi":"10.1097/FBP.0000000000000850","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000850","url":null,"abstract":"<p><p>Pre- and probiotics promote a diverse and functional gut microbiota and have demonstrated both anxiolytic and antidepressant effects; however, how synbiotic diet interacts with antidepressant medications has not been fully investigated. This study sought to evaluate the potential anxiolytic or antidepressant effects of a synbiotic diet in an avian model that presents homologies with treatment-resistant depression. In addition, we sought to evaluate the potential interaction of a synbiotic diet combined with select doses of ketamine. Socially raised Black Australorp chicks were given either standard or synbiotic feed for 7 days. At 7 days posthatch, chicks from each feed condition were administered either 0, 5, or 10 mg/kg/ml ketamine 15 min before a 90-min isolation stressor, which elicits distress vocalizations (DVocs) that temporally represent a panic-like phase followed by a depression-like phase. Saline-treated chicks given the synbiotic diet displayed significantly higher DVoc rates in the depression-like phase compared with saline-treated animals in the standard feed condition, indicative of attenuation of behavioral despair [F(1,22) = 5.45, P < 0.05]. Similarly, in the standard diet condition, ketamine 10 mg/kg produced elevated DVoc rates; however, under the synbiotic diet, both doses of ketamine produced a suppression of DVoc rates in the depression-like phase. These findings suggest that a synbiotic diet produces antidepressant-like effects in the model and a possible negative interaction between synbiotics and ketamine. While preliminary, the findings suggest the concurrent use of pre- and probiotic supplements and ketamine may produce contradictory effects and warrant further investigation.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991384","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}
Adam L Crane, Laurence E A Feyten, Alix J P Brusseau, Félixe Dumaresq Synnott, Indar W Ramnarine, Maud C O Ferrari, Grant E Brown
{"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":"https://doi.org/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":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991396","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}