Synapse (New York, N.y.)最新文献

{"title":"The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: a meta-analysis.","authors":"Hamid R Noori,&nbsp;Sarah Fliegel,&nbsp;Ines Brand,&nbsp;Rainer Spanagel","doi":"10.1002/syn.21581","DOIUrl":"https://doi.org/10.1002/syn.21581","url":null,"abstract":"<p><p>In vivo microdialysis has become a key method in investigating the dynamics of different neurotransmitter systems such as acetylcholine in the extracellular fluid. Depending on the sensitivity of the analytical method applied for measuring acetylcholine levels in brain dialysates, acetylcholinesterase (AChE) inhibitors are often used to increase the basal acetylcholine level up to a detectable magnitude. This artificial manipulation of the system questions the outcome of pharmacological studies and has led to a large number of experiments pursuing the appropriate physiological and pharmacological concentration of the AChE inhibitors in a range between 0.01 and 100 μM. However, the complexity of the action of these substances, particularly through the involvement of muscarinic autoreceptors and the induction of an autoinhibitory effect on acetylcholine release, did not allow this quest to be resolved completely and suggests the application of advanced mathematical methods for the evaluation of acetylcholine baseline levels. Here we performed a meta-analysis on published datasets of in vivo microdialysis measurements to assess the concentration-dependent effects of various AChE inhibitors on acetylcholine levels within the prefrontal cortex, nucleus accumbens, caudate putamen, and hippocampus in adult rats. In total 3255 rats were analyzed and we found that when compared with the minority of studies (14%) that did not use AChE inhibitors (these studies yielded basal levels between 0.55 and 2.71 nM depending on the brain site) an up to 350-fold increase in baseline values after the application of an inhibitor could be detected. Especially, the derivates neostigmine bromide and physostigmine sulfate seem to produce dramatic effects. Furthermore, concentration-dependent effects after the application of AChE inhibitors could not be established. In the case of neostigmine bromide an inverted concentration (0.1-10 μM)-response relationship was even detected. We conclude that although the presynaptic action of AChE inhibitors is well understood the nonphysiological and concentration-independent augmentation of the acetylcholine system requires the use of a standard protocol in order to produce replicable and comparable results. Our meta-analysis suggests the use of 0.1 μM neostigmine which produces an approximately 10-fold boost of brain baseline levels.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"893-901"},"PeriodicalIF":2.3,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30717161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of ischemic neuronal damage with [¹⁸F]BMS-747158-02, a mitochondrial complex-1 positron emission tomography ligand: small animal PET study in rat brain.","authors":"Dai Fukumoto,&nbsp;Shingo Nishiyama,&nbsp;Norihiro Harada,&nbsp;Shigeyuki Yamamoto,&nbsp;Hideo Tsukada","doi":"10.1002/syn.21584","DOIUrl":"https://doi.org/10.1002/syn.21584","url":null,"abstract":"<p><p>The acute and subacute ischemic neuronal damage in rat brain caused by photochemically induced thrombosis (PIT) was imaged using [¹⁸F]BMS-747158-02 ([¹⁸F]BMS) for mitochondrial complex-1 (MC-1) and [¹¹C](R)-PK11195 ([¹¹C](R)-PK) for peripheral benzodiazepine receptor [PBR; translocator protein] at preischemic \"Normal,\" 1 (day 1), and 7 days (day 7) after ischemic insult. When [¹⁸F]BMS was intravenously injected into \"Normal\" rat, it was rapidly taken up into the brain, in which it showed a homogeneous distribution, and the uptake was suppressed by rotenone, a specific MC-1 inhibitor. The specificity of [¹⁸F]BMS binding to MC-1 was also confirmed by living brain slice imaging. At day 1, [¹⁸F]BMS uptake was low in infarct and peri-infarct regions where neuronal damage was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. At day 7, the damaged areas determined using [¹⁸F]BMS revealed some discrepancy from those detected by TTC staining, suggesting that TTC stained not only surviving cells but also activated microglial cells in the peri-infarct region. This was also confirmed by [¹¹C](R)-PK imaging and immunohistochemical assessment with Iba1 antibody. In contrast, the uptake pattern of [¹⁸F]BMS was consistent with immunohistochemical assessment with NeuN antibody at both days 1 and 7. These results demonstrated that [¹⁸F]BMS could be a promising positron emission tomography ligand to assess the neuronal damage induced by ischemic insult in both acute and subacute phases.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"909-17"},"PeriodicalIF":2.3,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30770560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential role of serotonin projections from the dorsal and median raphe nuclei in phencyclidine-induced hyperlocomotion and fos-like immunoreactivity in rats.","authors":"Snezana Kusljic,&nbsp;Maarten Van Den Buuse","doi":"10.1002/syn.21580","DOIUrl":"https://doi.org/10.1002/syn.21580","url":null,"abstract":"<p><p>Altered brain serotonin activity is implicated in schizophrenia. We have previously shown differential involvement of serotonergic projections from the dorsal or median raphe nucleus in phencyclidine-induced hyperlocomotion in rats, a behavioral model of aspects of schizophrenia. Here we further investigated the effects of serotonergic lesions of the raphe nuclei on phencyclidine-induced hyperlocomotion by parallel assessment of Fos-like immunoreactivity (FLI), a marker of neuronal activation in the brain. Male Sprague-Dawley rats were anesthetized with pentobarbitone and stereotaxically microinjected with 5 μg of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into either the dorsal raphe (DRN) or median raphe nucleus (MRN). Two weeks after the surgery, rats with lesions of the MRN, but not those with lesions of the DRN, showed significant enhancement of the hyperlocomotion induced by injection of 2.5 mg/kg of phencyclidine. Rats with MRN lesions also showed significantly higher levels of FLI in the polymorphic layer of the dentate gyrus in the dorsal hippocampus (PoDG) when compared with sham-operated controls. Rats with lesions of the DRN showed significantly higher levels of FLI in the nucleus accumbens (NAcc). These results indicate that FLI in the PoDG, but not the NAcc, correlates with enhanced phencyclidine-induced locomotor hyperactivity in MRN-lesioned rats. These results support our previous studies suggesting a role of serotonergic projections from the MRN to the dorsal hippocampus in some of the symptoms of schizophrenia.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"885-92"},"PeriodicalIF":2.3,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30718311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No change in [¹¹C]CUMI-101 binding to 5-HT(1A) receptors after intravenous citalopram in human.","authors":"Lars H Pinborg,&nbsp;Ling Feng,&nbsp;Mette E Haahr,&nbsp;Nic Gillings,&nbsp;Agnete Dyssegaard,&nbsp;Jacob Madsen,&nbsp;Claus Svarer,&nbsp;Stig Yndgaard,&nbsp;Troels W Kjaer,&nbsp;Ramin V Parsey,&nbsp;Hanne D Hansen,&nbsp;Anders Ettrup,&nbsp;Olaf B Paulson,&nbsp;Gitte M Knudsen","doi":"10.1002/syn.21579","DOIUrl":"https://doi.org/10.1002/syn.21579","url":null,"abstract":"<p><p>The main objective of this study was to determine the sensitivity of [¹¹C]CUMI-101 to citalopram challenge aiming at increasing extracellular 5-HT. CUMI-101 has agonistic properties in human embryonic kidney 293 cells transfected with human recombinant 5-HT(1A) receptors (Hendry et al. [2011] Nucl Med Biol 38:273-277; Kumar et al. [2006] J Med Chem 49:125-134) and has previously been demonstrated to be sensitive to bolus citalopram in monkeys (Milak et al. [2011] J Cereb Blood Flow Metab 31:243-249). We studied six healthy individuals. Two PET-scans were performed on the same day in each individual before and after constant infusion of citalopram (0.15 mg/kg). The imaging data were analyzed using two tissue compartment kinetic modeling with metabolite corrected arterial input and Simplified Reference Tissue Modeling using cerebellum as a reference region. There was no significant difference in regional distribution volume or non-displaceable binding potential values before and after citalopram infusion. The mean receptor occupancy was 0.03 (range -0.14 to 0.17). Our data imply that [¹¹C]CUMI-101 binding is not sensitive to citalopram infusion in humans.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"880-4"},"PeriodicalIF":2.3,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30716993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mice lacking neuropeptide Y show increased sensitivity to cocaine.","authors":"Gunnar Sørensen,&nbsp;David P D Woldbye","doi":"10.1002/syn.21568","DOIUrl":"https://doi.org/10.1002/syn.21568","url":null,"abstract":"<p><p>There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction. Whether this is due to an observed compensatory increase in striatal dopamine transporter binding or an anxiogenic phenotype of the transgenic mice remains to be determined.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"840-3"},"PeriodicalIF":2.3,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21568","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40192643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal expression of stathmin 1 in brain tissue of patients with intractable temporal lobe epilepsy and a rat model.","authors":"Fenghua Zhao,&nbsp;Yida Hu,&nbsp;Ying Zhang,&nbsp;Qiong Zhu,&nbsp;Xiaogang Zhang,&nbsp;Jing Luo,&nbsp;Yali Xu,&nbsp;Xuefeng Wang","doi":"10.1002/syn.21567","DOIUrl":"https://doi.org/10.1002/syn.21567","url":null,"abstract":"<p><p>Microtubule dynamics have been shown to contribute to neurite outgrowth, branching, and guidance. Stathmin 1 is a potent microtubule-destabilizing factor that is involved in the regulation of microtubule dynamics and plays an essential role in neurite elongation and synaptic plasticity. Here, we investigate the expression of stathmin 1 in the brain tissues of patients with intractable temporal lobe epilepsy (TLE) and experimental animals using immunohistochemistry, immunofluorescence and western blotting. We obtained 32 temporal neocortex tissue samples from patients with intractable TLE and 12 histologically normal temporal lobe tissues as controls. In addition, 48 Sprague Dawley rats were randomly divided into six groups, including one control group and five groups with epilepsy induced by lithium chloride-pilocarpine. Hippocampal and temporal lobe tissues were obtained from control and epileptic rats on Days 1, 7, 14, 30, and 60 after kindling. Stathmin 1 was mainly expressed in the neuronal membrane and cytoplasm in the human controls, and its expression levels were significantly higher in patients with intractable TLE. Moreover, stathmin 1 was also expressed in the neurons of both the control and the experimental rats. Stathmin 1 expression was decreased in the experimental animals from 1 to 14 days postseizure and then significantly increased at Days 30 and 60 compared with the control group. Many protruding neuronal processes were observed in the TLE patients and in the chronic stage epileptic rats. These data suggest that stathmin 1 may participate in the abnormal network reorganization of synapses and contribute to the pathogenesis of TLE.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"781-91"},"PeriodicalIF":2.3,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40184797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of extrastriatal D2 in vivo specific binding of [¹⁸F](N-methyl)benperidol using PET.","authors":"Sarah A Eisenstein,&nbsp;Jon M Koller,&nbsp;Marilyn Piccirillo,&nbsp;Ana Kim,&nbsp;Jo Ann V Antenor-Dorsey,&nbsp;Tom O Videen,&nbsp;Abraham Z Snyder,&nbsp;Morvarid Karimi,&nbsp;Stephen M Moerlein,&nbsp;Kevin J Black,&nbsp;Joel S Perlmutter,&nbsp;Tamara Hershey","doi":"10.1002/syn.21566","DOIUrl":"https://doi.org/10.1002/syn.21566","url":null,"abstract":"<p><p>PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near-equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [¹⁸F]N-methylbenperidol ([¹⁸F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [¹⁸F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown. A composite MR-PET image was constructed across 14 healthy adult participants representing average NMB uptake 60 to 120 min after [¹⁸F]NMB injection. Regional peak radioactivity was identified using a peak-finding algorithm. FreeSurfer and manual tracing identified a priori regions of interest (ROI) on each individual's MR image and tissue activity curves were extracted from coregistered PET images. [¹⁸F]NMB binding potentials (BP(ND) s) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BP(ND) estimates were compared between Logan graphical methods and a three-compartment kinetic tracer model. Radioactivity and BP(ND) levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BP(ND) s. BP(ND) estimates for extrastriatal ROIs were highly correlated across kinetic and graphical methods. Our findings indicate that PET with [¹⁸F]NMB measures specific binding in extrastriatal regions, making it a viable radioligand to study extrastriatal D2R levels in healthy and diseased states.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"770-80"},"PeriodicalIF":2.3,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40184952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naloxone can act as an analgesic agent without measurable chronic side effects in mice with a mutant mu-opioid receptor expressed in different sites of pain pathway.","authors":"Shu-Husan Chou, Jen-Hsin Kao, Pao-Luh Tao, Ping-Yee Law, Horace H Loh","doi":"10.1002/syn.21555","DOIUrl":"10.1002/syn.21555","url":null,"abstract":"<p><p>Midbrain periaqueductal gray (PAG) and spinal cord dorsal horn are major action sites of opioid analgesics in the pain pathway. Our previous study has shown that opioid antagonists activate MORS196A-CSTA (a mutant of mu-opioid receptor) as full agonists in vitro cell models and naloxone showed antinociceptive effects after the expression of MORS196A-CSTA in the spinal cord in mice. The purpose of this study is to investigate the site-directed antinociceptive effects of naloxone in mice injected with dsAAV-MORS196A-CSTA-EGFP at spinal cord or at periaqueductal gray. MORS196A-CSTA-EGFP was administered to ICR mice using dsAAV as vector. We measured MORS196A-CSTA-EGFP expression by detecting the EGFP visualization with a fluorescence microscope. The antinociceptive effect of naloxone was determined by tail-flick test and hot plate test. Drug rewarding effect was evaluated by the conditioned place preference test. Naloxone (10 mg/kg, s.c.) elicited both supraspinal and spinal antinociceptive responses in mice injected with the virus at PAG while only spinal antinociceptive response was observed in mice injected with virus at dorsal horn region. Chronic naloxone treatment did not induce physical dependence or rewarding effect in mice injected with MORS196A-CSTA-EGFP in spinal cord or PAG. These data suggest that the observed naloxone-induced antinociceptive response is the consequence of the local expression of MORS196A-CSTA at specific sites of pain pathway. Injection of such MOR mutant and the systemic administration of naloxone can be a new strategy in the management of chronic pain without the various side effects associated with the use of morphine.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"694-704"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370265/pdf/nihms363392.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40155411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Affinity and selectivity of [¹¹C]-(+)-PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo.","authors":"Jean-Dominique Gallezot,&nbsp;John D Beaver,&nbsp;Roger N Gunn,&nbsp;Nabeel Nabulsi,&nbsp;David Weinzimmer,&nbsp;Tarun Singhal,&nbsp;Mark Slifstein,&nbsp;Krista Fowles,&nbsp;Yu-Shin Ding,&nbsp;Yiyun Huang,&nbsp;Marc Laruelle,&nbsp;Richard E Carson,&nbsp;Eugenii A Rabiner","doi":"10.1002/syn.21535","DOIUrl":"https://doi.org/10.1002/syn.21535","url":null,"abstract":"<p><p>Although [¹¹C]-(+)-PHNO has enabled quantification of the dopamine-D3 receptor (D3R) in the human brain in vivo, its selectivity for the D3R is not sufficiently high to allow us to disregard its binding to the dopamine-D2 receptor (D2R). We quantified the affinity of [¹¹C]-(+)-PHNO for the D2R and D3R in the living primate brain. Two rhesus monkeys were examined on four occasions each, with [¹¹C]-(+)-PHNO administered in a bolus + infusion paradigm. Varying doses of unlabeled (+)-PHNO were coadministered on each occasion (total doses ranging from 0.09 to 5.61 μg kg⁻¹). The regional binding potential (BP(ND) ) and the corresponding doses of injected (+)-PHNO were used as inputs in a model that quantified the affinity of (+)-PHNO for the D2R and D3R, as well as the regional fractions of the [¹¹C]-(+)-PHNO signal attributable to D3R binding. (+)-PHNO in vivo affinity for the D3R (K(d)/f(ND) ~0.23-0.56 nM) was 25- to 48-fold higher than that for the D2R (K(d)/f(ND) ~11-14 nM). The tracer limits for (+)-PHNO (dose associated with D3R occupancy ~10%) were estimated at ~0.02-0.04 μg kg⁻¹ injected mass for anesthetized primate and at 0.01-0.02 μg kg⁻¹ for awake human positron emission tomography (PET) studies. Our data enabled a rational design and interpretation of future PET studies with [¹¹C]-(+)-PHNO.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"489-500"},"PeriodicalIF":2.3,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of mirtazapine on sleep disturbance under neuropathic pain-like state.","authors":"Tatsuya Enomoto,&nbsp;Akira Yamashita,&nbsp;Kazuhiro Torigoe,&nbsp;Hiroshi Horiuchi,&nbsp;Shigeto Hirayama,&nbsp;Kae Nakahara,&nbsp;Makoto Yanase,&nbsp;Hiroyasu Sakai,&nbsp;Daigo Ikegami,&nbsp;Hiroshi Nagase,&nbsp;Tsutomu Suzuki,&nbsp;Masako Iseki,&nbsp;Eiichi Inada,&nbsp;Minoru Narita","doi":"10.1002/syn.21532","DOIUrl":"https://doi.org/10.1002/syn.21532","url":null,"abstract":"<p><p>Sleep disturbance has been reported to be one of the most frequent symptoms in patients suffered from severe pain. Benzodiazepines are effective and reduce anxiety in the hours after use, but the induced sleep tends to be less than ideal in quality, with increased Stages I-II and reduces Stages III-IV sleep. In the present study, we investigated sleep disturbance under a neuropathic pain-like state in mice using electroencephalogram (EEG)/electromyogram (EMG). In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase. Mirtazapine (MTZ) is an antidepressant, which is considered to enhance noradrenergic and serotonergic neurotransmission via antagonistic action at central α2-adrenergic autoreceptors and heteroreceptors. In the present binding study, MTZ showed higher affinity for histamine H₁ and serotonin 5-HT(2A/2C) receptors than other receptors, including α2-adrenergic receptor, in the mouse brain tissue. The thermal hyperalgesia and sleep disturbance following nerve ligation were almost completely alleviated by MTZ. These findings suggest that MTZ may improve the quality of sleep as well as control pain in patients with neuropathic pain mainly through histamine H₁- and serotonin 5-HT₂-receptor antagonistic actions.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"483-8"},"PeriodicalIF":2.3,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}