Behavioural Pharmacology最新文献

{"title":"5-HT2A receptor inverse agonist attenuates morphine withdrawal syndrome and its aversiveness in rats.","authors":"Ping-Hsun Tsai, Erica R Morales, Yvonne Y Reed, Hasan Qamar, Emily F Jones, Gopika Saji, Christopher P Ward, Ethan S Burstein, Georgina L Moreno, David H Malin","doi":"10.1097/FBP.0000000000000832","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000832","url":null,"abstract":"<p><p>This study explored a potential role for the 5-hydroxytryptamine2A (5-HT2A) serotonin receptor in opiate physical dependence. Rats were rendered opiate-dependent by 7 days of continuous subcutaneous (s.c.) morphine sulfate infusion. Pimavanserin is a selective 5-HT2A receptor inverse agonist in current medical use. A day after termination of drug infusion, rats were injected s.c. with 0.3 or 1.0 mg/kg pimavanserin or saline alone. A nondependent control group was infused with saline alone and injected with saline. One hour after injections, all rats were observed under blind conditions for somatically expressed spontaneous withdrawal signs. While both pimavanserin doses significantly reduced withdrawal signs in the dependent rats, the higher dose reduced those signs to the level exhibited by the nondependent group. In a second experiment, utilizing only nondependent, saline-infused rats, pimavanserin had no significant effect vs. saline injection on overall signs. A third experiment extended these findings to naloxone-precipitated morphine withdrawal. Relative to saline injection, pimavanserin, 1.3 mg/kg s.c., significantly reduced withdrawal signs precipitated by 0.3 mg/kg naloxone 1 h later. This effect was reconfirmed in a separate experiment. The pimavanserin injection also significantly attenuated the aversiveness of morphine withdrawal, as indicated by reduced conditioned avoidance of the chamber where precipitated withdrawal had occurred. These results indicate a major role for the 5-HT2A receptor in opiate physical dependence and withdrawal syndrome, suggesting this receptor as a potential therapeutic target.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109573","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":"https://doi.org/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 (KATP) 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/KATP pathways, and opioidergic and GABA receptors, respectively.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","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":"The effects of high fat diet consumption on morphine-induced constipation.","authors":"Nina M Beltran, Thelma I Garcia, Gabriela M Naime, Vanessa Minervini, Katherine M Serafine","doi":"10.1097/FBP.0000000000000831","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000831","url":null,"abstract":"<p><p>Opioids, prescribed for pain relief or as maintenance therapies for opioid use disorder, induce constipation, which can lead to medication compliance issues. However, it is not known how dietary manipulation might impact opioid-induced constipation. To test the hypothesis that eating a high fat diet exacerbates opioid-induced constipation, male and female Sprague-Dawley rats (n = 8/diet/sex) were fed either a low fat (standard) diet, a high fat/high carbohydrate diet, or a ketogenic diet. Rats were injected with either saline or morphine (1-10 mg/kg) and constipation was measured by counting fecal boli hourly for 6 h. Morphine-induced comparable constipation in all groups; however, rats eating a high fat/high carbohydrate or ketogenic diet produced significantly less feces following injections of saline or morphine as compared to rats eating a standard diet (P < 0.05). Dietary considerations might be important for patients prescribed opioid medications.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973741","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":"Slight and hidden hearing loss differentially affect short- and long-term memory in young rats.","authors":"Joëlle D Jagersma, Sonja J Pyott, Jocelien D A Olivier","doi":"10.1097/FBP.0000000000000828","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000828","url":null,"abstract":"<p><p>Mild forms of hearing loss (HL) have been linked to cognitive impairments in children, yet the neurobiological mechanisms underlying this connection remain unclear. Existing research using animal models mostly focuses on more severe levels of HL or investigates only limited aspects of cognition. To gain a broader understanding of how slight/hidden HL affects cognitive behaviors, we induced HL in 4-week-old Wistar rats through noise exposure. Auditory brainstem response measurements confirmed slight and hidden HL, but this auditory impairment did not alter the density of inner hair cells or their synapses with the spiral ganglion (primary auditory) neurons. Both short- and long- term memory formation were tested using the object location, novel object recognition, and social recognition task. Behaviorally, rats with slight/hidden HL performed better than normal hearing (NH) rats during short-term cognition tests. However, long-term memory was impaired in rats with slight/hidden HL when compared to NH controls. Slight/hidden HL also did not consistently affect (social) exploration. In conclusion, this study demonstrates that slight and hidden HL differentially affect short- and long-term cognitive processes in an animal model of early (noise-induced) HL, without affecting (social) exploration. These results suggest a nuanced relationship between slight and hidden HL and both short- and long-term memory formation, underscoring the importance of broader cognitive phenotyping and further investigation into the neurobiological structures linking hearing impairment with cognitive function.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962315","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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-16","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":"Gabapentin and D-cycloserine alone and in combination with naloxone in methadone-maintained humans responding under a naloxone novel-response discrimination procedure.","authors":"Lauren R Fitzgerald, Nichole C Stanley, Joseph B Guise, Christopher S Cargile, Michael J Mancino, Alison H Oliveto","doi":"10.1097/FBP.0000000000000823","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000823","url":null,"abstract":"<p><p>The present study examined the impact of the N-type calcium channel blocker gabapentin (GBP) and the partial glycine agonist D-cycloserine (CYC) to attenuate the behavioral effects of naloxone in opioid-dependent humans responding under a naloxone discrimination procedure. Methadone-maintained participants were trained to distinguish between a low dose of naloxone (0.15 mg/70 kg, i.m.; i.e., drug A) and placebo (i.e. drug B) under an instructed novel-response drug discrimination procedure, in which participants identify the drug condition as 'A', 'B', or 'N' (neither A nor B - 'novel'). Once the discrimination was acquired, doses of CYC (0, 500, and 625 mg) and GBP (0, 100, 200, and 400 mg) each alone and in combination with the training dose of naloxone were tested. GBP alone produced only placebo-appropriate responding and did not significantly alter naloxone discrimination when coadministered with naloxone, though it modestly reduced naloxone-induced visual analog scale ratings of drug 'strength'. CYC alone also produced predominantly placebo-appropriate responding and did not modulate naloxone-appropriate responding, but increased ratings of bad effects and decreased ratings of like placebo relative to naloxone alone at the 500 mg dose. These null findings regarding the modulation of naloxone discrimination highlight the limited efficacy of GBP and CYC in this context, contributing to the understanding of pharmacological interactions with opioid antagonists and their potential implications for opioid withdrawal treatment.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062018","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":"Self-synergy antinociceptive effect of diclofenac: effect of peripheral inhibition of nitric oxide synthase.","authors":"Jorge Elías Torres-López, Mayra Martínez-Martínez, Leonor Ivonne Parra-Flores","doi":"10.1097/FBP.0000000000000824","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000824","url":null,"abstract":"<p><p>This study was conducted to characterize the interaction between the systemic and local peripheral antinociceptive effect of diclofenac, a nonsteroidal anti-inflammatory drug. As well as the effect of local peripheral administration of NG-nitro-L-arginine methyl ester (L-NAME) - a nitric oxide synthesis inhibitor - on the antinociceptive effect of diclofenac. The antinociceptive effect of diclofenac in a fixed-ratio combination of local or intraperitoneal delivery diclofenac was evaluated using the formalin test. Pain-related behavior was quantified in terms of the number of flinches of the injected paw with formalin. Isobolographic analysis was employed to characterize the interaction between the two routes. ED30 values were estimated for each route, and an isobologram was constructed. Diclofenac and its fixed-ratio combination produced a dose-dependent antinociceptive effect in the second phase, but not in the first phase of the formalin test. The analysis revealed that the simultaneous administration of diclofenac through the two routes was synergistic. Pretreatment of the injured paw with L-NAME partially blocked local, systemic, and simultaneous local and systemic diclofenac-induced antinociception. The obtained results show a synergism after simultaneous administration of diclofenac through two different routes. In addition, it is found that either the local or systemic antinociceptive effect of diclofenac involves the activation of the nitric oxide pathway at the peripheral level.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762529","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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-02","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":"The effects of cannabinoid agonism on auditory discrimination.","authors":"Danielle Nykanen, Hannah Stiffler, Merrick Bay, Cameron Goldie, Shinnyi Chou, Natashia Swalve","doi":"10.1097/FBP.0000000000000811","DOIUrl":"10.1097/FBP.0000000000000811","url":null,"abstract":"<p><p>Recent evidence suggests that cannabis can impair simple auditory processes, and these alterations might be due to cannabinoid agonism. The effect of cannabinoid agonism on relatively complex processes such as auditory discrimination is unknown. The goal of this study was to examine the impact of WIN 55,212-2, a CB 1 receptor and CB 2 receptor agonism, on auditory discrimination using a go/no-go task. Twenty-two male and female Sprague-Dawley rats were initially trained to lever-press for sucrose to either a pure tone or white noise cue in a go/no-go paradigm, where rats were reinforced for lever-pressing during one cue and punished for lever-pressing during the other auditory cue. After criterion performance was met, rats were then injected with WIN 55,212-2 at 1.2 mg/kg, 3 mg/kg, or a corresponding vehicle (saline) and were tested on auditory discrimination. On day 3, active lever-pressing was higher in both the low- and high-dose WIN groups compared with the saline group. Overall lever-pressing decreased over time in the high-dose WIN 55,212-2 group. There were no effects of the drug on discrimination or errors, suggesting that cannabinoid agonism did not negatively affect auditory discrimination. This is the first study to examine the impact of cannabinoids on the discrimination of tones, finding that, contrary to previous research, the low and high doses of WIN 55,212-2 did not adversely impact auditory-linked behaviors.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"71-75"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880987","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 Psilocybe cubensis alkaloids on depressive-like behavior in mice exposed to maternal separation with respect to hippocampal gene expression and DNA methylation of Slc6a4 and Nr3c1.","authors":"Eghbal Jasemi, Ali Razmi, Salar Vaseghi, Shayan Amiri, S Mahmoud A Najafi","doi":"10.1097/FBP.0000000000000813","DOIUrl":"10.1097/FBP.0000000000000813","url":null,"abstract":"<p><p>Maternal separation as an early life stress can lead to long-lasting deleterious effects on cognitive and behavioral functions, and the mood state. On the other hand, Psilocybe cubensis (as one of the most well-known magic mushrooms) may be beneficial in the improvement or the treatment of neuropsychiatric disorders. In the present study, we aimed to investigate the effect of P. cubensis extract (PCE) on depressive-like and anxiety-like behaviors, and locomotor activity in mice exposed to early maternal separation. Also, we assessed the expression and methylation level of Slc6a4 and Nr3c1 in the hippocampus. Maternal separation was done in postnatal days (PNDs) 2-18. PCE was intraperitoneally injected at the dose of 20 mg/kg at PND 60, and our tests were done at days 1, 3, and 10, of administration. The results showed that maternal separation significantly induced depressive-like behavior in the forced swim test and anxiety-like behavior in the open field test (OFT). Also, maternal separation decreased locomotor activity in the OFT. In addition, maternal separation decreased the expression and increased the methylation level of both Slc6a4 and Nr3c1 in the hippocampus. However, PCE significantly reversed all these effects. In conclusion, it seems that P. cubensis affects serotonergic signaling via altering Slc6a4 expression and methylation level in the hippocampus of mice. The effect of P. cubensis on Nr3c1 expression and methylation level may also lead to alter the function of the hypothalamus-pituitary-adrenal axis and the stress response in mice exposed to maternal separation.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"115-126"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447898","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}