Behavioural Pharmacology最新文献

{"title":"Cannabidiol and cognition: a literature review of human randomized controlled trials.","authors":"Jyotpal Singh, Chase J Ellingson, M Abdullah Shafiq, Jane Alcorn, J Patrick Neary","doi":"10.1097/FBP.0000000000000837","DOIUrl":"10.1097/FBP.0000000000000837","url":null,"abstract":"<p><p>Cannabidiol (CBD) is a phytocannabinoid without intoxicating properties. While CBD can improve neurophysiological functions and subjective symptoms, its effect on cognitive function remains unclear. We summarized the available randomized controlled trials investigating CBD administration and cognitive function. A review of the literature was conducted using the following keywords on PubMed/Medline: (cannabis OR cannabidiol OR cannabinoid OR CBD OR Δ 9 -tetrahydrocannabinol OR tetrahydrocannabinol) AND (neurology OR brain OR psychiatric OR neuroscience OR psychology OR cognition) AND (human) AND (randomized controlled trial OR RCT). The search yielded 1038 articles with 36 total included for this literature review. The articles included healthy participants, neurological disease, psychiatric disease, psychosis, paranoia, schizophrenia, and drug-use disorders. Studies with healthy participants included a variety of dosing strategies, suggesting an effect on cognitive function and sleep quality. In Parkinson's disease, 75-300 mg CBD resulted in mild improvements in daily life activities. Decreases in subjective anxiety were found in patients with psychiatric disease using CBD doses ranging from 300 to 400 mg. In patients with psychosis and paranoia, 600 mg CBD showed inconsistent results in cognitive function. In patients with schizophrenia, up to 1000 mg CBD per day had minimal effects on cognition. Finally, up to 800 mg CBD had minimal effects on cognitive function in patients with substance use disorders. The findings are limited by utilization of acute dosing, variations in CBD dose, and different routes of administration. Standardized dosing and CBD formulations are needed to assess its efficacy for improving cognition.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"203-216"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257298","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":"Cannabidiol on aggression in betta fish ( Betta splendens ).","authors":"Mariangel Varela, Charlotte C Gard, Wiebke J Boeing","doi":"10.1097/FBP.0000000000000822","DOIUrl":"10.1097/FBP.0000000000000822","url":null,"abstract":"<p><p>Cannabidiol (CBD) was first isolated in the 1940s and its drug structure was established in the 1960s. It has risen significantly in popularity since then and has been observed to reduce inflammation and anxiety in patients. CBD is easy to obtain and consume, therefore, its common use is rising and has spread to use in pets and children. Few studies have focused on the use of CBD as a solution to aggression. In our study, we tested if CBD is effective in reducing aggression in Siamese fighting fish ( Betta splendens ) induced by territorial interactions. Betta fish were exposed to controls (water or acetone) and CBD treatments ranging from low, medium, and high (2, 10, and 20 mg CBD/L, respectively), and their behaviors after the visual introduction of an intruder fish were recorded. CBD reduced the odds of aggressive behavior in treated fish. Seventy-five percent of all control fish exhibited aggressive behaviors, while only 17% of CBD-treated fish displayed aggression. Especially, the low CBD dose seemed effective at preventing aggressive behaviors but fish also appeared more lethargic than in any of the other treatments. However, when CBD-treated fish displayed aggressive behaviors, CBD did not appear to reduce the amount of time fish spent being aggressive compared to aggressive fish that did not receive any CBD treatment. While the long-term effects of CBD still have to be examined, our study indicates that CBD might be effective in reducing aggression in Betta fish and potentially other pets.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"226-233"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763001","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":"Curcumin mitigates memory deficits induced by subcutaneous aluminum nanoparticle administration through modulation of hippocampal brain-derived neurotrophic factor and Akt signaling pathways.","authors":"Samaneh Reiszadeh Jahromi, Zahra Keikhosravi, Roksana SoukhakLari, Maryam Moosavi","doi":"10.1097/FBP.0000000000000825","DOIUrl":"10.1097/FBP.0000000000000825","url":null,"abstract":"<p><p>Research has indicated a strong link between exposure to aluminum (Al) and the development of Alzheimer's disease (AD). Given the rising use of Al nanoparticles, which are far more neurotoxic than Al, it is noteworthy to investigate the possible protective properties of natural substances. Curcumin, an important component of turmeric, has demonstrated neuroprotective effects in some animal studies. The main objective of this study was to examine the protective effects of curcumin on the memory deficit induced by subcutaneous aluminum oxide nanoparticles (Al-NP) administration in mice. Additionally, considering the roles of the hippocampal brain-derived neurotrophic factor (BDNF) and Akt pathway in AD pathology, their levels were evaluated. Adult male Swiss mice (SWR/J) were administered Al-NP (10 mg/kg/s.c.) with or without curcumin (2.5, or 25 mg/kg/P.O) for 10 days. Memory and anxiety-like behavior were assessed using passive avoidance and elevated plus maze tasks, respectively. Western blot analysis was employed to measure hippocampal BDNF and Akt proteins in the hippocampus. The findings revealed that Al-NP induced memory impairment in mice, whereas curcumin at 25 mg/kg prevented this memory deficit. Additionally, Al-NP significantly reduced the hippocampal BDNF and phosphorylated Akt levels, while curcumin increased BDNF and phosphorylated Akt to a nonsignificant level compared to the control group. These results not only suggest the neuroprotective properties of curcumin but also suggest a possible association between hippocampal BDNF and Akt signaling in the neuroprotective mechanism of this compound against Al-NP toxicity.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"290-299"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956166","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":"Deciphering the antinociceptive and anti-inflammatory effects of pelargonidin through L-arginine/nitric oxide/cyclic GMP/ATP-sensitive potassium channel signaling pathway and gamma-aminobutyric acid/opioidergic receptors.","authors":"Sona Hamidi, Fatemeh Abbaszadeh, Amir Kiani, Mohammad Hosein Farzaei, Sajad Fakhri","doi":"10.1097/FBP.0000000000000830","DOIUrl":"10.1097/FBP.0000000000000830","url":null,"abstract":"<p><p>There are complex dysregulated pathways behind the pathogenesis of pain and inflammation. Because most of the present drugs have certain side effects or are not effective enough, providing novel multitargeting and potent therapeutic agents is of particular importance. This study investigates the antinociceptive effects of pelargonidin, an anthocyanin derived from various plants, through the modulation of the L-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/ATP-sensitive potassium channel (K ATP ) signaling pathway. We also evaluated the anti-inflammatory role of pelargonidin passing through gamma-aminobutyric acid (GABA) and opioidergic receptors. Two experimental models were utilized. In the carrageenan model, 42 rats were divided into control, diclofenac, and three doses of pelargonidin (3, 6, and 9 mg/kg). In addition, two groups received pelargonidin 9 mg/kg + naloxone and pelargonidin 9 mg/kg + flumazenil. For the formalin model, 90 male mice were assigned to control, diclofenac, and three doses of pelargonidin, and 10 groups receiving L-arginine, S-nitroso- N -acetylpenicillamine (SNAP), N (gamma)-nitro-L-arginine methyl ester (L-NAME), glibenclamide, and sildenafil individually or alongside pelargonidin 9 mg/kg. Our results indicated that pelargonidin significantly decreased inflammation and pain in a dose-dependent manner. Notably, groups of pelargonidin 9 mg/kg + naloxone and pelargonidin 9 mg/kg + flumazenil diminished pelargonidin's anti-inflammatory effectiveness, underscoring the significant role of these receptors. Mechanistically, it was shown that the antinociceptive effects of pelargonidin were mediated by the NO signaling pathway. While L-NAME and glibenclamide reduced pelargonidin's antinociceptive efficacy, supplementation with sildenafil and SNAP enhanced the effect. This investigation demonstrated that pelargonidin possesses dose-dependent antinociceptive and anti-inflammatory actions through L-arginine/NO/cGMP/K ATP pathways, and opioidergic and GABA receptors, respectively.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"312-321"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953259","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":"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":"https://doi.org/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-HT1A neurons, 5-HT7 neurons, drosophila insulin-like protein neurons, and pigment dispersing factor neurons modulate locomotor activity independent of METH response. The mushroom body, 5-HT7 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-HT7 neurons appear to mediate METH-induced locomotor response most directly.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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/KATP 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":"https://doi.org/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 (KATP) signaling pathways, opioidergic, and benzodiazepine receptors.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-07","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-07","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","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":"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":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antidepressant-like activity of ketamine in the rat chronic mild stress model requires activation of cortical 5-HT 1A receptors.","authors":"Ronan Depoortère, Mariusz Papp, Piotr Gruca, Ewa Litwa, Magdalena Lason, Dominika Biała, Adrian Newman-Tancredi","doi":"10.1097/FBP.0000000000000809","DOIUrl":"10.1097/FBP.0000000000000809","url":null,"abstract":"<p><p>Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.) administration or local administration in the prefrontal cortex (PFC). However, the receptor mechanisms underlying these effects remain to be clarified and may involve activation of serotonin 5-HT 1A receptors, as previously found in experiments using the forced swim test. The present study explored the contribution of PFC 5-HT 1A receptors in ketamine's RAAD activity in the CMS model. Ketamine (10 mg/kg i.p.) reversed CMS-induced sucrose consumption and working memory (NOR test) deficits. Notably, unilateral PFC microinjections of a 5-HT 1A receptor antagonist, WAY-100635 (2 µg), prevented the antidepressant-like and pro-cognitive activity of systemic ketamine on sucrose consumption and working memory deficits. These data indicate that the RAAD activity of ketamine in the rat CMS model requires activation of PFC 5-HT 1A receptors. They also reinforce the notion that drugs that directly activate PFC 5-HT 1A receptors could constitute an alternative to ketamine as a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits in depressed patients, but without ketamine's troublesome side-effects and requirements for in-patient supervision.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"182-188"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881072","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}