Behavioural Pharmacology最新文献_第9页

CB2 agonist mitigates cocaine-induced reinstatement of place preference and modulates the inflammatory response in mice. CB2 激动剂能减轻可卡因诱导的小鼠位置偏好恢复并调节炎症反应。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-13 DOI: 10.1097/fbp.0000000000000759

Oualid Abboussi, Zmarak Ahmad Khan, Hind Ibork, Simo S Zulu, William Daniels, Khalid Taghzouti, Tim G Hales

{"title":"CB2 agonist mitigates cocaine-induced reinstatement of place preference and modulates the inflammatory response in mice.","authors":"Oualid Abboussi, Zmarak Ahmad Khan, Hind Ibork, Simo S Zulu, William Daniels, Khalid Taghzouti, Tim G Hales","doi":"10.1097/fbp.0000000000000759","DOIUrl":"https://doi.org/10.1097/fbp.0000000000000759","url":null,"abstract":"Chronic exposure to cocaine is known to have profound effects on the brain, leading to the dysregulation of inflammatory signalling pathways, the activation of microglia, and the manifestation of cognitive and motivational behavioural impairments. The endocannabinoid system has emerged as a potential mediator of cocaine's deleterious effects. In this study, we sought to investigate the therapeutic potential of the cannabinoid CB2 receptor agonist, JWH-133, in mitigating cocaine-induced inflammation and associated motivational behavioural alterations in an in vivo model. Our research uncovered compelling evidence that JWH-133, a selective CB2 receptor agonist, exerts a significant dampening effect on the reinstatement of cocaine-induced conditioned place preference. This effect was accompanied by notable changes in the neurobiological landscape. Specifically, JWH-133 administration was found to upregulate Δ-FOSB expression in the nucleus accumbens (Nac), elevate CX3CL1 levels in both the ventral tegmental area and prefrontal cortex (PFC), and concurrently reduce IL-1β expression in the PFC and NAc among cocaine-treated animals. These findings highlight the modulatory role of CB2 cannabinoid receptor activation in altering the reward-seeking behaviour induced by cocaine. Moreover, they shed light on the intricate interplay between the endocannabinoid system and cocaine-induced neurobiological changes, paving the way for potential therapeutic interventions targeting CB2 receptors in the context of cocaine addiction and associated behavioural deficits.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"71 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692458","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}

引用次数: 0

MA-5 ameliorates autism-like behavior in mice prenatally exposed to valproic acid. MA-5改善了出生前接触丙戊酸的小鼠的自闭症样行为。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-10-01 DOI: 10.1097/FBP.0000000000000758

Yasuhiro Nakagami, Mina Nishi

{"title":"MA-5 ameliorates autism-like behavior in mice prenatally exposed to valproic acid.","authors":"Yasuhiro Nakagami, Mina Nishi","doi":"10.1097/FBP.0000000000000758","DOIUrl":"10.1097/FBP.0000000000000758","url":null,"abstract":"Indole-3-acetic acid is a common naturally occurring auxin in plants. A synthesized derivative of this compound, 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid also called mitochonic acid 5 (MA-5), has shown to increase the survival ratio of fibroblasts from patients with mitochondrial disease under stress-induced conditions. Further studies verified its efficacy in pathological models, such as an ischemia-reperfusion model, possibly by increasing ATP production. However, the efficacy of MA-5 in mental disorders, such as anxiety, schizophrenia, and autism spectrum disorders (ASD), has not been investigated. Our study focused on examining the effect of MA-5 in a mouse model of ASD induced by prenatal exposure to valproic acid (VPA). VPA exposure significantly deteriorated the level of anxiety and exploratory behavior in an open field test. We fed mice an MA-5-containing diet for 5 weeks and observed an improvement in the above behavior in the MA-5-fed groups. The efficacy of MA-5 was also observed in the elevated plus maze and three-chambered tests. These findings suggest that MA-5 could potentially be used to treat ASD, especially in patients with mitochondrial dysfunction.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"34 8","pages":"488-493"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420332","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}

引用次数: 0

Effects of acute and chronic nicotine administration on probability discounting. 急性和慢性尼古丁给药对概率折扣的影响。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-03-23 DOI: 10.1097/FBP.0000000000000753

Katya A Nolder, Karen G Anderson

{"title":"Effects of acute and chronic nicotine administration on probability discounting.","authors":"Katya A Nolder, Karen G Anderson","doi":"10.1097/FBP.0000000000000753","DOIUrl":"10.1097/FBP.0000000000000753","url":null,"abstract":"Nicotine use is a continuing public health concern. Smokers are more likely to make risky or maladaptive decisions compared to nonsmokers, so the relation between nicotine and risky choice warrants further investigation. Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer and can be assessed through a probability-discounting procedure. Acute nicotine administration has been shown to alter risky choice, but because the everyday smoker uses nicotine repeatedly, more research on chronic administration is needed and would allow for assessment of tolerance or sensitization of any effects. The present study examined effects of acute and repeated nicotine administration on probability discounting. Sprague-Dawley rats were used as subjects and the probability-discounting task involved discrete-trial choices between a small, certain reinforcer and a larger, uncertain reinforcer. The probability of larger-reinforcer delivery decreased across blocks within each session. Acute nicotine (0.1-1.0 mg/kg) administration dose-dependently increased risky choice, increased lose-stay ratios (a measure of response perseveration), and decreased reinforcement frequency. Tolerance to nicotine's effects on larger-reinforcer choice was observed after repeated 1.0 mg/kg nicotine administration. The results of the present study add to the existing literature that acute nicotine administration increases risky choice and demonstrates that tolerance to this effect develops after chronic exposure to the drug. Possible behavioral mechanisms behind this effect are discussed, as are suggestions for future research on nicotine and risky choice.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"468-476"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145556","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}

引用次数: 0

Histamine and its H 1 receptors in the ventral pallidum mediate formalin-induced pain-related behaviors through this region and spinal cord opioid receptors. 腹侧苍白球中的组胺及其H1受体通过该区域和脊髓阿片受体介导福尔马林诱导的疼痛相关行为。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-03-06 DOI: 10.1097/FBP.0000000000000724

Morteza Asgharieh-Ahari, Esmaeal Tamaddonfard, Amir Erfanparast, Farhad Soltanalinejad-Taghiabad

{"title":"Histamine and its H 1 receptors in the ventral pallidum mediate formalin-induced pain-related behaviors through this region and spinal cord opioid receptors.","authors":"Morteza Asgharieh-Ahari, Esmaeal Tamaddonfard, Amir Erfanparast, Farhad Soltanalinejad-Taghiabad","doi":"10.1097/FBP.0000000000000724","DOIUrl":"10.1097/FBP.0000000000000724","url":null,"abstract":"Many structures of the central nervous system recruit different neurotransmitters in pain processing. This study focused on the contribution of histamine and its H 1 receptors in the ventral pallidum (VP) in mediating pain-triggered behaviors. Intra-VP microinjection of histamine and 2-pyridylethylamine (2-PEA, a histamine H 1 receptor agonist) at the same doses of 0.5 and 1 µg/200 nl reduced both the first and second phases of licking/biting duration as well as flinching number induced by intra-plantar (ipl) injection of formalin (2.5%, 50 µl). Premicroinjection of mepyramine (a histamine H 1 antagonist, 2 µg/200 nl) into the VP antagonized the suppressive effects of 1 µg/200 nl histamine and 2-PEA on licking/biting and flinching behaviors. The possible mechanisms of the above-mentioned pain-reducing effects were followed by intra-VP and intrathecal administration of naloxone (an opioid receptor antagonist). Naloxone (2 µg/200 nl) preadministration into the VP inhibited attenuating effects of histamine and 2-PEA on both the licking/biting and flinching behaviors, whereas intrathecal injection of naloxone only inhibited their suppressing effects on flinching behavior. None of the treatments used in this study altered the animal's motor activity. The obtained results may reveal the role of histamine and its activated H 1 receptor in the VP in suppressing the pain behaviors caused by formalin. Opioid receptors in the VP and spinal cord may contribute to these functions.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"457-467"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194135","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}

引用次数: 0

The role of l -arginine/NO/cGMP/K ATP channel pathway in the local antinociceptive effect of berberine in the rat formalin test. l-精氨酸/NO/cGMP/K ATP通道通路在黄连素大鼠福尔马林局部镇痛作用中的作用。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-03-20 DOI: 10.1097/FBP.0000000000000721

Milad Rahemi, Shokooh Mohtadi, Hossein Rajabi Vardanjani, Mohammad Javad Khodayar

{"title":"The role of l -arginine/NO/cGMP/K ATP channel pathway in the local antinociceptive effect of berberine in the rat formalin test.","authors":"Milad Rahemi, Shokooh Mohtadi, Hossein Rajabi Vardanjani, Mohammad Javad Khodayar","doi":"10.1097/FBP.0000000000000721","DOIUrl":"10.1097/FBP.0000000000000721","url":null,"abstract":"Berberine is an isoquinoline alkaloid naturally produced by several types of plants. Berberine has extensive pharmacological effects, such as anti-diabetic, anti-inflammatory, and antioxidant effects. In the current study, we assess the antinociceptive effects of berberine and its association with the l -arginine ( l -Arg)/NO/cGMP/K ATP channel pathway via intraplantar administration in rats. To examine the antinociceptive properties of berberine, the formalin test was conducted. The number of rat paw flinches was counted for an h. l -Arg (precursor of nitric oxide, 3-30 μ g/paw), l -NAME (NO synthase inhibitor, 10 and 100 μ g/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200 μ g/paw), and glibenclamide (ATP-sensitive potassium channel blocker, 10 and 30 μ g/paw) were locally injected, respectively, into the right hind paws of rats as a pre-treatment before berberine injection to understand how the l -Arg/NO/cGMP/K ATP pathway plays a role in the antinociceptive effect of berberine. The ipsilateral injection of berberine into the right paw (0.1-10 0 μ g/paw) showed a dose-dependent antinociceptive effect in both the first and second phases of the formalin test, almost similar to morphine (25 μ g/paw). Intraplantar injection of l -Arg (30 µg/paw) increased the antinociceptive effect of berberine in the second phase. In addition, injection of l -NAME, methylene blue, and glibenclamide caused a reduction in the antinociceptive effect of berberine throughout the second phase in a dose-dependent manner. However, the antinociceptive effects of berberine in the first phase of the rat formalin test were not affected by this pathway. As a novel local antinociceptive agent, berberine can exert a peripheral antinociceptive effect via the l -Arg/NO/cGMP/K ATP channel pathway.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"449-456"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194134","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}

引用次数: 0

Chronic pharmacological activation of SERCA with CDN1163 affects spatial cognitive flexibility but not attention and impulsivity in mice. CDN1163对SERCA的慢性药理学激活影响小鼠的空间认知灵活性，但不影响注意力和冲动性。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-10-01 DOI: 10.1097/FBP.0000000000000756

Benjamin Klocke, Carter Moore, Hayden Ott, Pothitos M Pitychoutis

{"title":"Chronic pharmacological activation of SERCA with CDN1163 affects spatial cognitive flexibility but not attention and impulsivity in mice.","authors":"Benjamin Klocke, Carter Moore, Hayden Ott, Pothitos M Pitychoutis","doi":"10.1097/FBP.0000000000000756","DOIUrl":"10.1097/FBP.0000000000000756","url":null,"abstract":"Intracellular calcium (Ca2+) homeostasis is critical for many neural processes, including learning, memory and synaptic plasticity. The sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) is among the key regulators that preserve Ca2+ homeostasis in neurons. SERCAs comprise a set of ubiquitously expressed Ca2+ pumps that primarily function to sequester cytosolic Ca2+ into endoplasmic reticular stores. As SERCA has been implicated in the neurobiology of several neuropsychiatric and neurodegenerative diseases, pharmacological harnessing of its function is critical in understanding SERCA's role in brain physiology and pathophysiology. In the current study, we employed the Morris water maze and 5-choice serial reaction time task (5-CSRTT) to investigate the effects of chronic pharmacological activation of SERCA, using the small allosteric SERCA activator CDN1163, on spatial learning and memory, and executive functioning in naive C57BL/6J mice. Our data show that chronic pharmacological SERCA activation with CDN1163 (20 mg/kg) selectively impairs spatial cognitive flexibility and reversal learning in the Morris water maze while leaving executive functions such as attention and impulsivity intact. Present findings contribute to the growing field of the role of SERCA function in the brain and behavior and expand current knowledge on the use of the small allosteric activator CDN1163 as an investigational tool to study the role of SERCA in regulating neurobehavioral processes and as a potential therapeutic candidate for debilitating brain disorders.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"34 8","pages":"477-487"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420331","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}

引用次数: 0

Methodological approach: using a within-subjects design in the marble burying assay. 方法论方法：在大理石掩埋试验中使用受试者内部设计。

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-12-01 Epub Date: 2023-08-31 DOI: 10.1097/FBP.0000000000000752

Kaitlyn J Partridge, Ruth Olson, Todd M Hillhouse

{"title":"Methodological approach: using a within-subjects design in the marble burying assay.","authors":"Kaitlyn J Partridge, Ruth Olson, Todd M Hillhouse","doi":"10.1097/FBP.0000000000000752","DOIUrl":"10.1097/FBP.0000000000000752","url":null,"abstract":"In 2016, the National Institutes of Health mandated the use of both male and female mice in funded research. The use of both sexes is an important variable to consider; however, it comes with negative consequences such as increased animal expenses. One way to combat these negatives is to explore the option of using a within-subjects design (repeated measures) in behavioral assays that historically use a between-subjects design. Our study aimed to determine if a within-subjects design can be utilized in the marble burying assay. The marble burying assay is used as a tool for screening putative anxiolytic compounds as the assay is thought to measure obsessive-compulsive disorder- or anxiety-like behaviors. First, we compared the effects of sex and digging medium (corn cob or Sani Chip) on the number of marbles buried using CD-1 mice. Second, we determined if mice would continue to bury marbles after repeated exposures to the test arena. Lastly, we tested three positive controls (buspirone, ketamine, and fluoxetine). We found that mice buried significantly more marbles within Sani Chip digging medium, and no sex differences were observed. Next, the number of marbles buried and locomotor activity remained consistent across four test sessions. The positive controls buspirone (3.2-10 mg/kg) ketamine (32 mg/kg), and fluoxetine (10 mg/kg) decreased the number of marbles buried using the within-subjects design. These data suggest that a within-subjects design is optimal for the marble burying assay as it will reduce the number of animals and increase statistical power.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"494-499"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152043","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}

引用次数: 0

Minocycline as a potential anxiolytic drug: systematic review and meta-analysis of evidence in murine models 米诺环素作为一种潜在的抗焦虑药物：小鼠模型证据的系统回顾和荟萃分析

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-11-21 DOI: 10.1097/fbp.0000000000000754

L. P. Iglesias, Nicia Soares, L. Asth, Fabrício A Moreira, D. Aguiar

{"title":"Minocycline as a potential anxiolytic drug: systematic review and meta-analysis of evidence in murine models","authors":"L. P. Iglesias, Nicia Soares, L. Asth, Fabrício A Moreira, D. Aguiar","doi":"10.1097/fbp.0000000000000754","DOIUrl":"https://doi.org/10.1097/fbp.0000000000000754","url":null,"abstract":"Minocycline is a tetracycline antibiotic with off-label use as an anti-inflammatory drug. Because it can cross the blood-brain barrier, minocycline has been proposed as an alternative treatment for psychiatric disorders, in which inflammation plays an important role. However, its beneficial effects on anxiety disorders are unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy of minocycline as an anxiolytic drug in preclinical models. We performed a PubMed search according to the PRISMA guidelines and PICOS strategy. The risk of bias was evaluated using the SYRCLE tool. We included studies that determined the efficacy of minocycline in animal models of anxiety that may involve exposures (e.g. stressors, immunomodulators, injury). Data extracted included treatment effect, dose range, route of administration, and potential mechanisms for the anxiolytic effect. Meta-analysis of twenty studies showed that minocycline reduced anxiety-like behavior in rodents previously exposed to stress or immunostimulants but not in exposure-naïve animals. This effect was not associated with the dose administered or treatment duration. The mechanism for the anxiolytic activity of minocycline may depend on its anti-inflammatory effects in the brain regions involving anxiety. These suggest that minocycline could be repurposed as a treatment for anxiety and related disorders and warrants further evaluation.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"30 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252477","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}

引用次数: 0

Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride 研究非典型抗精神病药物氨磺必利的鉴别刺激特性的内在机制

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-11-16 DOI: 10.1097/fbp.0000000000000760

T. Donahue, T. Hillhouse, Kevin A. Webster, Richard Young, Eliseu O. De Oliveira, Joseph H. Porter

{"title":"Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride","authors":"T. Donahue, T. Hillhouse, Kevin A. Webster, Richard Young, Eliseu O. De Oliveira, Joseph H. Porter","doi":"10.1097/fbp.0000000000000760","DOIUrl":"https://doi.org/10.1097/fbp.0000000000000760","url":null,"abstract":"Amisulpride is an atypical benzamide antipsychotic/antidepressant, whose mechanism of action is thought to depend mainly on dopamine D2/3 receptor activity, but also with some serotonin 5-HT2B/7 effects. The present study examined the role of D2/3 receptors and 5-HT2B/7 receptors in amisulpride’s discriminative stimulus. Selective agonists and antagonists of the above receptors were tested in adult, male C57BL/6 mice trained to discriminate 10 mg/kg amisulpride from vehicle in a two-lever drug discrimination assay. After acquisition of the two-lever discrimination, the amisulpride generalization curve yielded an ED50 = 0.56 mg/kg (95% CI = 0.42–0.76 mg/kg). Substitution tests found that the D2/3 antagonist raclopride (62.7% Drug Lever Responding), D2/3 agonist quinpirole (56.6% DLR), 5-HT7 agonist LP-44 (50.1% DLR) and 5-HT7 antagonist SB-269970 (36.7% DLR) produced various degrees of partial substitution for the amisulpride stimulus, whereas the 5-HT2B agonist BW 723C86 (17.9% DLR) and 5-HT2B antagonist SB-204741 (21.1% DLR) yielded negligible amisulpride-like effects. In combination tests with amisulpride, quinpirole decreased percent responding from 98.3% to 57.0% DLR, LP-44 decreased percent responding from 97.6% to 76.7% DLR, and BW 723C86 reduced percent responding from 95.66% to 74.11% DLR. Taken together, the results from stimulus generalization and antagonism studies suggest that amisulpride has a complex discriminative cue that involves mainly mixed D2/3 receptor antagonist/agonist effects and, to a lesser degree, mixed 5-HT7 receptor agonist/antagonist and perhaps 5-HT2B receptor antagonist effects.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"9 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139269865","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}

引用次数: 0

Antinociceptive and adverse effects of morphine:ketamine mixtures in rats 吗啡：氯胺酮混合物对大鼠的抗镇痛作用和不良反应

IF 1.6 4区心理学

Behavioural Pharmacology Pub Date : 2023-11-16 DOI: 10.1097/fbp.0000000000000761

Conor D. Strumberger, Evangeline J. D’Epagnier, Kevin H. Nguyen, John D. Rogers, Matthew P. Meyer, Yashmita Malhotra, Jillian E. Hinman, Elisabeth L. Jansen, Vanessa Minervini

{"title":"Antinociceptive and adverse effects of morphine:ketamine mixtures in rats","authors":"Conor D. Strumberger, Evangeline J. D’Epagnier, Kevin H. Nguyen, John D. Rogers, Matthew P. Meyer, Yashmita Malhotra, Jillian E. Hinman, Elisabeth L. Jansen, Vanessa Minervini","doi":"10.1097/fbp.0000000000000761","DOIUrl":"https://doi.org/10.1097/fbp.0000000000000761","url":null,"abstract":"Prescription opioids are the gold standard for treating moderate to severe pain despite their well-documented adverse effects. Of all prescription medications, opioids are abused most widely, and fatal overdoses have reached epidemic levels. One strategy for improving the margin of safety of opioids is combining them with non-opioid drugs to decrease the opioid dose needed for pain relief, thereby reducing adverse effects that occur with larger doses. The N-methyl-D-aspartate receptor antagonist ketamine has been used safely as an analgesic but only under a very limited range of conditions. The current studies characterized the antinociceptive, behavioral suppressant, and gastrointestinal effects of morphine and ketamine alone and in mixtures to determine their interaction in 24 adult male Sprague–Dawley rats (n = 8 per assay). Given alone, both morphine and ketamine produced antinociception, decreased responding for food, and reduced gastrointestinal transit (i.e. produced constipation). The effects of morphine:ketamine mixtures generally were additive, except for the antinociceptive effects of 1:1 mixtures for which the difference in slope (i.e. non-parallel shift) between the observed and predicted effects suggested synergy at smaller doses and additivity at larger doses. The potency of morphine to produce constipation was not enhanced by administration of morphine:ketamine mixtures with antinociceptive effects. The nature of the interaction between morphine and ketamine for adverse effects such as dependence, withdrawal, abuse, or respiratory depression remains unknown but also might be related to the ratio of each drug in mixtures. It will be important to identify conditions that produce the largest potential therapeutic window in humans.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"35 10","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139269483","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}

引用次数: 0