| 1 | Neuropsychopharmacology 2006 Apr 31: 795-803 |
|---|---|
| PMID | 16052245 |
| Title | Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice. |
| Abstract | Cannabidiol, a nonpsychoactive constituent of the Cannabis sativa plant, has been reported to act as an agonist of the vanilloid 1 channel in the transient receptor potential family (TRPV1),同时也抑制了水解和细胞uptake of the endogenous cannabinoid anandamide. Cannabidiol has also been reported to have potential as an antipsychotic. We investigated the effect of cannabidiol on sensorimotor gating deficits in mice induced by the noncompetitive NMDA receptor antagonist, MK-801. Sensorimotor gating is deficient in psychotic disorders such asschizophreniaand may be reliably measured by prepulse inhibition (PPI) of the startle response in rodents and humans. MK-801 (0.3-1 mg/kg i.p.) dose dependently disrupted PPI while cannabidiol (1-15 mg/kg i.p.), when administered with vehicle, had no effect on PPI. Cannabidiol (5 mg/kg i.p.) successfully reversed disruptions in PPI induced by MK-801 (1 mg/kg i.p.), as did the atypical antipsychotic clozapine (4 mg/kg i.p.). Pretreatment with capsazepine (20 mg/kg i.p.) prevented the reversal of MK-801-induced disruption of PPI by cannabidiol, providing preliminary evidence thatTRPV1受体参与了MK-801诱导的大麻二酚的感觉运动剖道缺陷。 |
| SCZ Keywords | schizophrenia |
| 2 | 生物。Psychiatry 2006 Mar 59: 508-15 |
| PMID | 16199010 |
| Title | Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. |
| Abstract | Knockout (KO) mice invalidated for the dopamine transporter (DAT) constitute a powerful animal model of neurobiological alterations associated with hyperdopaminergia relevant toschizophreniaand attention-deficit/hyperactivity disorder (ADHD). Because of continuously increasing evidence for a neuromodulatory role of endocannabinoids in dopamine-related pathophysiological responses, we assessed endocannabinoid signaling in DAT KO mice and evaluated the ability of endocannabinoid ligands to normalize behavioral deficits, namely spontaneous hyperlocomotion in these mice. 在DAT KO小鼠中，我们发现配胺水平明显降低，特别是在多巴胺神经末端区域的纹状体中。此外，三种不同的间接内源性大麻素激动剂，选择性肛门胺的再摄取抑制剂AM404和VDM11以及脂肪酸酰胺水酶抑制剂AA5HT，减弱了Dat Ko小鼠中自发性超循环。AM404，VDM11和AA5HT的降压运动作用通过瞬态受体电位香草的共同给药显着减弱（TRPV1) antagonist capsazepine but not the selective cannabinoid type 1 (CB1)receptor antagonist AM251. Interestingly,TRPV1binding was increased in the striatum of DAT KO mice, while CB1 receptor binding was unaffected. These data indicate a dysregulated striatal endocannabinoid neurotransmission associated with hyperdopaminergic state. Restoring endocannabinoid homeostasis in active synapses might constitute an alternative therapeutic strategy for disorders associated with hyperdopaminergia. In this process,TRPV1receptors seem to play a key role and represent a novel promising pharmacological target. |
| SCZ Keywords | schizophrenia |
| 3 | ADV。经验。医学生物。2011 -1 704：987-1009 |
| PMID | 21290337 |
| Title | TRP渠道和精神疾病。 |
| Abstract | 抑郁和schizophreniaare major psychiatric disorders that cause much human suffering. Current treatments have major limitations and new drug targets are eagerly sought. Study of transient receptor potential (TRP) channels in these disorders is at an early stage and the potential of agents that activate or inhibit these channels remains speculative. The findings that TRPC6 channels promote dendritic growth and are selectively activated by hyperforin, the key constitutent of St John's wort, suggest that TRPC6 channels might prove to be a new target for antidepressant drug development. There is now considerable evidence thatTRPV1拮抗剂具有抗焦虑活性，但没有直接的证据表明它们具有抗抑郁活性。也没有直接证据表明TRP渠道在schizophrenia。但是，TRPC渠道参与神经元发展和基本突触机制的发现，以及TRPV1channels play a role in central dopaminergic and cannabinoid mechanisms is suggestive of potential roles of these channels inschizophrenia。Investigation of TRP channels in psychiatric disorders holds the promise of yielding further understanding of the aetiology of psychiatric disorders and the development of new drug treatments. |
| SCZ Keywords | schizophrenia |
| 4 | Inflamm. Res. 2012 Nov 61: 1283-91 |
| PMID | 22820944 |
| Title | 过量的组胺H？反向激动剂粘液剂增加了热疼痛阈值。 |
| Abstract | Pitolisant (BF2.649) is a selective inverse agonist for the histamine H(3) receptor and was developed for the treatment of excessive daytime sleepiness in Parkinson disease, narcolepsy, andschizophrenia。由于H（3） - 配体可以减轻炎症性疼痛，因此我们在炎症性和神经性疼痛模型中测试了垂体。材料和处理：在Zymosan诱导的炎症和神经性疼痛的避免神经损伤模型中测试了垂体和不同H（3）受体反向激动剂的行为效应。 Responses to mechanical and thermal stimuli were determined. Calcium imaging was performed with primary neuronal cultures of dorsal root ganglions. Clinically relevant doses of pitolisant (10 mg/kg) had no relevant effect on mechanical or thermal pain thresholds in all animal models. Higher doses (50 mg/kg) dramatically increased thermal but not mechanical pain thresholds. Neither ciproxifan nor ST-889 altered thermal pain thresholds. In peripheral sensory neurons high concentrations of pitolisant (30-500 ?M), but not ciproxifan, partially inhibited calcium increases induced by capsaicin, a selective activator of transient receptor potential vanilloid receptor 1 (TRPV1）。高剂量的酸糖浆诱导强烈的体温过低。 The data show a dramatic effect of high dosages of pitolisant on the thermosensory system, which appears to be H(3) receptor-independent. |
| SCZ Keywords | schizophrenia |
| 5 | 行为。Brain Res. 2014 Oct 272: 55-65 |
| PMID | 24975423 |
| Title | Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour. |
| Abstract | 用瞬态受体电位香草素1处理新生大鼠（TRPV1）通道激动剂，辣椒素，会产生表达的感觉神经元的终生丧失TRPV1channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects withschizophrenia。本研究的目的是研究用辣椒素处理为新生儿的成年大鼠的大脑和行为反应。发现在被视为新生儿的大鼠中发现的大脑变化持续到成年后（12周），但在老鼠（16-18周）中却较少。在这些大鼠8和12周龄的这些大鼠中发现了声音惊吓的预硫次抑制（PPI），而不是在动物模型中常见的赤字schizophrenia。Subjects withschizophreniaalso have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role ofTRPV1频道进schizophreniais worthy of investigation. |
| SCZ Keywords | schizophrenia |
| 6 | Schizophr. Res. 2014 Mar 153: 150-9 |
| PMID | 24556469 |
| Title | 大麻素和香草素药物对精神分裂症的动物模型的阳性和阴性症状的影响：SHR菌株。 |
| Abstract | Studies have suggested that the endocannabinoid system is implicated in the pathophysiology ofschizophrenia。我们最近报道说，自发性高血压大鼠（SHR）表现出社会互动的不足，这是通过非典型抗精神病药改善的。此外，SHRS显示超取代 - 由非典型和典型的抗精神病药恢复。这些结果表明，这种菌株可能有助于研究负面症状（通过社交互动减少）和正症状（通过超置态建模）的负面症状有用。schizophreniaand the effects of potential drugs with an antipsychotic profile. The aim of this study was to investigate the effects of WIN55-212,2 (CB1/CB2 agonist), ACEA (CB1 agonist), rimonabant (CB1 inverse agonist), AM404 (anandamide uptake/metabolism inhibitor), capsaicin (agonistTRPV1) and capsazepine (antagonistTRPV1)社会互动和运动控制rol animals (Wistar rats) and SHRs. The treatment with rimonabant was not able to alter either the social interaction or the locomotion presented by Wistar rats (WR) and SHR at any dose tested. The treatment with WIN55-212,2 decreased locomotion (1mg/kg) and social interaction (0.1 and 0.3mg/kg) of WR, while the dose of 1mg/kg increased social interaction of SHR. The treatment with ACEA increased (0.3mg/kg) and decreased (1mg/kg) locomotion of both strain. The administration of AM404 increased social interaction and decreased locomotion of SHR (5mg/kg), and decreased social interaction and increased locomotion in WR (1mg/kg). The treatment with capsaicin (2.5mg/kg) increased social interaction of both strain and decreased locomotion of SHR (2.5mg/kg) and WR (0.5mg/kg and 2.5mg/kg). In addition, capsazepine (5mg/kg) decreased locomotion of both strains and increased (5mg/kg) and decreased (10mg/kg) social interaction of WR. Our results indicate that theschizophrenia-like behaviors displayed by SHR are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment ofschizophrenia。 |
| SCZ Keywords | schizophrenia |
| 7 | 生理学。行为。2014年2月125日：38-44 |
| PMID | 24291382 |
| Title | The effects of juvenile capsaicin desensitization in rats: behavioral impairments. |
| Abstract | Capsaicin desensitization leads to behavioral changes, some of which are related toschizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentiallyschizophrenia感觉器官有关的障碍在浇注,摩托r activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 �C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related toschizophrenia。We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model ofschizophrenia。 |
| SCZ Keywords | schizophrenia |
| 8 | Mod Trends Pharmacopsychiatri 2015 -1 30: 80-93 |
| PMID | 26436415 |
| Title | Supraspinal Transient Receptor Potential Subfamily V Member 1 (TRPV1) in Pain and Psychiatric Disorders. |
| Abstract | The transient receptor potential subfamily V member 1 (TRPV1) belongs to the diverse transient receptor potential (TRP) family of cation channels. It was first characterized in primary afferent fibres as a receptor for capsaicin. PeripheralTRPV1在伤害感受中具有非常描述的作用。然而，TRPV1现在被认为具有更广泛的分布和功能，具有上脊柱/大脑TRPV1已知可以调节疼痛处理。最近，采用组织学，遗传和药理方法的研究提供了证据表明TRPV1also modulates brain neurobiology and behaviours related to anxiety, depression andschizophrenia。Key brain regions involved inTRPV1-mediated modulation of pain and affect include the periaqueductal grey, hippocampus and medial prefrontal cortex. Thus,TRPV1in the brain is emerging as an important molecular substrate which is dually implicated in both pain and psychiatric disorders, and represents a novel therapeutic target for these conditions and their comorbidity. |
| SCZ Keywords | schizophrenia |
| 9 | Neurosci. Lett. 2016 Mar 616: 170-6 |
| PMID | 26836139 |
| Title | Slow synaptic transmission mediated by TRPV1 channels in CA3 interneurons of the hippocampus. |
| Abstract | Metabotropic glutamate receptors (mGluRs) modulate various neuronal functions in the central nervous system. Many studies reported that mGluRs have linkages to neuronal disorders such asschizophreniaand autism related disorders, indicating that mGluRs are involved in critical functions of the neuronal circuits. To study this possibility further, we recorded mGluR-induced synaptic responses in the interneurons of the CA3 stratum radiatum using rat hippocampal organotypic slice cultures. Electrical stimulation in the CA3 pyramidal cell layer evoked a slow inward current in the interneurons at a holding potential of -70mV in the presence of antagonists for AMPA/kainate receptors, NMDA receptors, GABAA receptors and GABAB receptors. The slow inward current was blocked in the absence of extracellular calcium, suggesting that this was a synaptic response. The slow excitatory postsynaptic current (EPSC) reversed near 0mV, reflecting an increase in a non-selective cationic conductance. The slow EPSC is mediated by group I mGluRs, as it was blocked by AP3, a group I mGluR antagonist. Neither a calcium chelator BAPTA nor a phospholipase C (PLC) inhibitor U73122 affected the slow EPSC. La(3+), a general TRP channel blocker or capsazepine, a selectiveTRPV1channel antagonist significantly suppressed the slow EPSC. DHPG, a selective group I mGluRs agonist induced an inward current, which was suppressed by capsazepine. These results indicate that in the interneurons of the hippocampal CA3 stratum radiatum group I mGluRs activateTRPV1频道进dependently of PLC and intracellular Ca(2+), resulting in the slow EPSC in the interneurons. |
| SCZ Keywords | schizophrenia |
| 10 | Chin J Physiol 2016 Feb 59: 21-32 |
| PMID | 26875559 |
| Title | Involvement of TRPV1 in the Olfactory Bulb in Rimonabant-Induced Olfactory Discrimination Deficit. |
| Abstract | 利莫那班是公认的大麻素CB ?receptor antagonist/inverse agonist. Rimonabant not only antagonizes the effects induced by exogenous cannabinoids and endocannabinoids at CB? receptors, it also exerts several pharmacological and behavioral effects independent of CB? receptor inactivation. For example, rimonabant can function as a low-potency mixed agonist/antagonist of the transient receptor potential vanilloid receptor 1 (TRPV1）。Hence, it is important to explain the underlying mechanisms of the diverse physiological effects induced by rimonabant with caution. Interestingly, CB? receptor has recently been suggested to play a role in olfactory functions. Olfaction not only is involved in food intake, visual perception and social interaction, but also is proposed as a putative marker forschizophrenia和自闭症。因此，本研究旨在调查CB是否？受体和TRPV1在嗅觉功能中发挥了作用。我们首先使用遗传破坏方法来检查CB的作用？嗅觉功能中的受体，发现CB？敲除小鼠表现出嗅觉歧视不足。但是，重要的是要指出这些CB？敲除小鼠尽管具有正常的移动性，但在嗅觉觅食和新颖的物体探索任务中表现出缺陷。这些结果表明，在CB中，对气味和无味物体的一般探索行为受到损害？淘汰小鼠。接下来，我们求助于检查CB的作用的药理方法？受体和TRPV1in olfactory functions. We found that the short-term administration of rimonabant, injected systemically or directly into the olfactory bulb (OB), impaired olfactory discrimination that was rescued by theTRPV1在野生型小鼠中，通过相同的Rimonabant途径进行拮抗剂辣椒粉（CPZ）。这些结果表明TRPV1in the OB is involved in rimonabant-induced olfactory discrimination deficit. However, the rimonabant and/or CPZ treatments neither affected locomotivity nor general exploratory behaviors in wild-type mice. Finally, the acute systemic administration of rimonabant, unlike the short-term administration regimen, did not affect olfactory discrimination. Taken together, this study not only is the first one, to the best of our knowledge, suggests that the olfactoryTRPV1plays a role in olfactory functions, but also provides a possible mechanism for the olfactory discrimination deficit induced by rimonabant. |
| SCZ Keywords | schizophrenia |