JOURNAL OF PHARMACOLOGICAL SCIENCES
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2019
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IF 2.439
Kai Zhang,Jing Lu,Lei Yao
Cedrol, mainly derived from Juniperus virginiana L. essential oil, has been demonstrated the anxiolytic effect, although its mechanism of action is still not fully established. In the present study, male ICR mice were submitted to the elevated plus maze (EPM) and light–dark box (LDB) tests to investigate the putative mechanism of anxiolytic effect. WAY100635 (5-HT 1A receptor antagonist), flumazenil (benzodiazepine receptor antagonist), SCH23390 (dopamine D 1 receptor antagonist) or sulpiride (dopamine D 2 /D 3 receptor antagonist) were used in the behavioral experiment to determine the mechanism of action of cedrol. Subsequently, the monoamine neurotransmitter levels were evaluated after behavioral tests. The data suggest that no significant effect in behavioral parameters were observed after sole intraperitoneal (i.p.) injection of antagonists compared to saline group. The anxiolytic effect of cedrol in behavioral procedures was blocked by either WAY100635 or flumazenil. The anxiolytic effect of cedrol (1200 mg/kg) was effectively antagonized by SCH23390 (0.125 mg/kg). Furthermore, cedrol decreased the DA and NE levels in hippocampus, striatum and hypothalamus. The present findings suggest that the dopaminergic system (D 1 receptor) rather than serotoninergic or GABAergic system may potentially be involved in the modulation of cedrol-induced anxiolytic-like behaviors in mice.
研究领域:
药理学
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神经科学
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行为学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE RESEARCH
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2011
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IF 2.096
Haiyan Xu,Ruirui Chen,Xiaoyan Cai,Defu He
Neostriatum plays an important role in the pathophysiology of Parkinson's disease (PD). However, the changes of sensitivity of dopamine receptors of neostriatal neurons in PD have been less addressed in vivo . In the present study, systemic exposure to paraquat and maneb induced Parkinsonian symptoms and neuronal loss of substantia nigra pars compacta. Using single-unit recording methods, three types of neostriatal neurons were recorded including medium spiny-like neurons, large aspiny-like neurons and fast-spiking interneurons. In the exposed rats, increased firing activity of neostriatal neurons was revealed when compared to control rats. Following D1 receptor agonist, SKF38393 and D2 receptor agonist, LY171555 iontophoretically administrated respectively, effects of increase and decrease in firing activity were both observed in neostriatal neurons. However, stronger inhibitory effects of activating D1 receptors and weaker excitatory effects of activating D2 receptors were found in the exposed rats as compared to controls. It indicated that differential changes of sensitivity of D1 and D2 receptors in Parkinson's disease were related to the modulation of the imbalance between D1-receptor-dependent striatonigral direct pathway and D2-receptor-dependent striatopallidal indirect pathway. Our results illustrate the electrophysiological changes of in vivo neostriatal neurons in Parkinson's disease, thereby providing insight into the regulatory mechanisms of dopamine-mediated physiology.
研究领域:
神经科学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2020
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IF 3.943
Zhao-Yan Cheng,Qing-Peng Xia,Yu-Hui Hu,Chen Wang,Ling He
Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. Dopamine is an important catecholaminergic neurotransmitter that controls movement, reward, motivation, and cognition. Recently, dopamine receptors were reported to regulate immune system in both periphery and central nervous system. However, whether dopamine D1 receptor (DRD1) activation could improve neuroinflammation in AD conditions remains unknown. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a potent and selective DRD1 agonist A-68930 on Aβ 1-42 -induced mice. Here we showed that intraperitoneal injection of A-68930 significantly ameliorated Aβ 1–42 -induced cognitive dysfunction in mice. Moreover, both in vivo and in vitro data showed that A-68930-induced DRD1 activation significantly inhibited NLRP3 inflammasome-dependent neuroinflammation induced by Aβ 1–42 , and this effect may be mediated by the activation of AMPK/autophagy signaling pathway, which enhanced NLRP3 inflammasome degradation and thus decreased the secretion of IL-1β and IL-18. The present study suggests that A-68930-induced DRD1 signaling efficiently alleviates Aβ 1–42 -induced cognitive impairment and neuroinflammation in mice and BV2 cells, and DRD1 may become a promising therapeutic target for AD.
研究领域:
神经科学
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药理学
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神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2023
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IF 14.5
Yue Zhang,Jingwen Gao,Na Li,Peng Xu,Shimeng Qu,Jinqian Cheng,Mingrui Wang,Xueru Li,Yaheng Song,Fan Xiao,Xinyu Yang,Jihong Liu,Hao Hong,Ronghao Mu,Xiaotian Li,Youmei Wang,Hui Xu,Yuan Xie,Tianming Gao,Guangji Wang,Jiye Aa
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
研究领域:
神经科学
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药理学
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精神病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2022
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IF 3.197
Tianyi Yang,Guang Yue,Yu Ge,Yue Zhang,Peng Xu,Youmei Wang,Bo Li,Bin Di
Nitrous oxide (N 2 O) has a long history of abuse, but its abuse mechanism has not been clear yet. This research aimed at the possibility of mesolimbic dopaminergic system (MLDS) involved in the rewarding effect of N 2 O. In this work, the rewarding behavior of N 2 O in mice was evaluated using a typical gas-administered conditioned place preference (CPP) procedure. SCH 23390, a Dopamine D1 receptor (D1R) antagonist, and Haloperidol, a Dopamine D2 receptor (D2R) antagonist were administered during CPP to evaluate the role of dopamine receptors in the N 2 O-induced CPP. The accompanying changes in phosphorylation of extracellular signal-regulated kinase (ERK) in MLDS related brain regions, including the ventral tegmental area (VTA), caudate putamen (CPu), prefrontal cortex (PFC), and nucleus accumbens (NAc) were measured to assess the neural plasticity changes in the CPP mice by Western blot analysis. Results revealed that 60% N 2 O induced CPP in the gas-administered mice and promoted the ERK phosphorylation (p-ERK) in the NAc and CPu during the test session of the CPP test. Pretreatment of SCH 23390 (0.5 mg/kg) inhibited the acquisition of N 2 O-induced CPP and the enhanced p-ERK in NAc. It suggested that Dopamine D1 receptor may play an important role in the acquisition of N 2 O-induced CPP and the accompanied ERK activation in the NAc, which provide insight into the molecular mechanism in the rewarding properties of nitrous oxide.
研究领域:
神经科学
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药理学
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行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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