Synapse (New York, N.y.)最新文献

{"title":"Effect of transient blockade of N-methyl-D-aspartate receptors at neonatal stage on stress-induced lactate metabolism in the medial prefrontal cortex of adult rats: role of 5-HT1A receptor agonism.","authors":"Takashi Uehara, Hiroko Itoh, Tadasu Matsuoka, Dan Rujescu, Just Genius, Tomonori Seo, Tomiki Sumiyoshi","doi":"10.1002/syn.21529","DOIUrl":"https://doi.org/10.1002/syn.21529","url":null,"abstract":"Decreased activity of the medial prefrontal cortex (mPFC) has been considered a basis for core symptoms of schizophrenia, an illness associated with a neurodevelopmental origin. Evidence from preclinical and clinical studies indicates that serotonin (5‐HT)1A receptors play a crucial role in the energy metabolism of the mPFC. This study was undertaken to determine (1) if transient blockade of N‐methyl‐D‐aspartate receptors during the neonatal stage inhibit energy demands in response to stress, as measured by extracellular lactate concentrations, in the mPFC at the young adult stage, and (2) if tandospirone, a 5‐HT1A partial agonist, reverses the effect of the neonatal insult on energy metabolism. Male pups received MK‐801 (0.20 mg/kg) on postnatal days (PDs) 7–10. On PD 63, footshock stress‐induced lactate levels were measured using in vivo microdialysis technique. Tandospirone (0.1, 1.0, and 5.0 mg/kg) was administered once daily for 14 days before the measurement of lactate levels. Neonatal MK‐801 treatment suppressed footshock stress‐induced lactate production in the mPFC, but not caudate‐putamen, whereas basal lactate levels were not significantly changed in either brain region. The MK‐801‐induced suppression of footshock stress‐induced lactate production in the mPFC was attenuated by tandospirone at 1.0mg/kg/day, but not 0.1 or 5.0 mg/kg/day, which is an effect antagonized by coadministration of WAY‐100635, a selective 5‐HT1A antagonist. These results suggest a role for impaired lactate metabolism in some of the core symptoms of schizophrenia, for example, negative symptoms and cognitive deficits. The implications for the ability of 5‐HT1A agonism to ameliorate impaired lactate production in the mPFC of this animal model are discussed. Synapse, 2012. © 2011 Wiley Periodicals, Inc.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"408-17"},"PeriodicalIF":2.3,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967750","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 the triple reuptake inhibitor amitifadine on extracellular levels of monoamines in rat brain regions and on locomotor activity.","authors":"Krystyna Golembiowska,&nbsp;Magdalena Kowalska,&nbsp;Frank P Bymaster","doi":"10.1002/syn.21531","DOIUrl":"https://doi.org/10.1002/syn.21531","url":null,"abstract":"<p><p>Major depressive disorder is a prevalent disease, and current pharmacotherapy is considered to be inadequate. It has been hypothesized that a triple reuptake inhibitor (TRI) that activates dopamine (DA) neurotransmission in addition to serotonin and norepinephrine (NE) circuitries may result in enhanced antidepressant effects. Here, we investigated the pharmacological effects of a serotonin-preferring TRI-amitifadine (EB-1010, formerly DOV 21947). The effects of amitifadine (10 mg/kg ip.) on extracellular concentrations of monoamines and their metabolites in rat brain regions were investigated using the in vivo microdialysis technique. The effects of amitifadine on locomotor activity and stereotyped behavior were also evaluated. A major metabolite of amitifadine, the 2-lactam compound, was investigated for inhibition of monoamine uptake processes. Amitifadine markedly and persistently increased extracellular concentrations of serotonin, NE, and DA in prefrontal cortex. The extracellular concentrations of DA were also increased in the DA-rich areas striatum and nucleus accumbens. The extracellular concentrations of the metabolites of serotonin, 5-hydroxyindoleacetic acid, and DA, 3,4-dihydroxyphenylacetic and homovanillic acid, were also markedly decreased in brain regions. Amitifadine did not increase locomotor activity or stereotypical behaviors over a broad dose range. The lactam metabolite of amitifadine weakly inhibited monoamine uptake. Thus, amitifadine increased extracellular concentrations of serotonin, NE, and DA, consistent with TRI. Although amitifadine significantly increased DA in the nucleus accumbens, it did not induce locomotor hyperactivity or stereotypical behaviors. The enhancement of serotonin, NE, and DA in rat brain regions associated with depression suggest that amitifadine may have novel antidepressant activity.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"435-44"},"PeriodicalIF":2.3,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967254","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":"Synaptic vesicle recycling is enhanced by torsinA that harbors the DYT1 dystonia mutation.","authors":"Yasuhiro Kakazu,&nbsp;Jin-Young Koh,&nbsp;K W David Ho,&nbsp;Pedro Gonzalez-Alegre,&nbsp;N Charles Harata","doi":"10.1002/syn.21534","DOIUrl":"https://doi.org/10.1002/syn.21534","url":null,"abstract":"<p><p>Early-onset generalized dystonia, DYT1, is caused by a mutation in the gene encoding the evolutionarily conserved AAA+ ATPase torsinA. Synaptic abnormalities have been implicated in DYT1 dystonia, but the details of the synaptic pathophysiology are only partially understood. Here, we demonstrate a novel role for torsinA in synaptic vesicle recycling, using cultured hippocampal neurons from a knock-in mouse model of DYT1 dystonia (ΔE-torsinA) and live-cell imaging with styryl FM dyes. Neurons from heterozygous ΔE-torsinA mice released a larger fraction of the total recycling pool (TRP) during a single round of electrical stimulation than did wild-type neurons. Moreover, when the neurons were subjected to prior high activity, the time course of release was shortened. In neurons from homozygous mice, these enhanced exocytosis phenotypes were similar, but in addition the size of the TRP was reduced. Notably, when release was triggered by applying a calcium ionophore rather than electrical stimuli, neither a single nor two ΔE-torsinA alleles affected the time course of release. Thus, the site of action of ΔE-torsinA is at or upstream of the rise in calcium concentration in nerve terminals. Our results suggest that torsinA regulates synaptic vesicle recycling in central neurons. They also indicate that this regulation is influenced by neuronal activity, further supporting the idea that synaptic abnormalities contribute to the pathophysiology of DYT1 dystonia.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"453-64"},"PeriodicalIF":2.3,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967265","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":"Nicotinic acetylcholine receptors in rat forebrain that bind ¹⁸F-nifene: relating PET imaging, autoradiography, and behavior.","authors":"Kasia M Bieszczad, Ritu Kant, Cristian C Constantinescu, Suresh K Pandey, Hideki D Kawai, Raju Metherate, Norman M Weinberger, Jogeshwar Mukherjee","doi":"10.1002/syn.21530","DOIUrl":"10.1002/syn.21530","url":null,"abstract":"<p><p>Nicotinic acetylcholine receptors (nAChRs) in the brain are important for cognitive function; however, their specific role in relevant brain regions remains unclear. In this study, we used the novel compound ¹⁸F-nifene to examine the distribution of nAChRs in the rat forebrain, and for individual animals related the results to behavioral performance on an auditory-cognitive task. We first show negligible binding of ¹⁸F-nifene in mice lacking the β2 nAChR subunit, consistent with previous findings that ¹⁸F-nifene binds to α4β2* nAChRs. We then examined the distribution of ¹⁸F-nifene in rat using three methods: in vivo PET, ex vivo PET and autoradiography. Generally, ¹⁸F-nifene labeled forebrain regions known to contain nAChRs, and the three methods produced similar relative binding among regions. Importantly, ¹⁸F-nifene also labeled some white matter (myelinated axon) tracts, most prominently in the temporal subcortical region that contains the auditory thalamocortical pathway. Finally, we related ¹⁸F-nifene binding in several forebrain regions to each animal's performance on an auditory-cued, active avoidance task. The strongest correlations with performance after 14 days training were found for ¹⁸F-nifene binding in the temporal subcortical white matter, subiculum, and medial frontal cortex (correlation coefficients, r > 0.8); there was no correlation with binding in the auditory thalamus or auditory cortex. These findings suggest that individual performance is linked to nicotinic functions in specific brain regions, and further support a role for nAChRs in sensory-cognitive function.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"418-34"},"PeriodicalIF":0.0,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292694/pdf/nihms349039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967386","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":"In vivo dopaminergic and behavioral responses to acute cocaine are altered in adenosine A(2A) receptor knockout mice.","authors":"Lisa Wells,&nbsp;Jolanta Opacka-Juffry,&nbsp;Donald Fisher,&nbsp;Catherine Ledent,&nbsp;Susanna Hourani,&nbsp;Ian Kitchen","doi":"10.1002/syn.21527","DOIUrl":"https://doi.org/10.1002/syn.21527","url":null,"abstract":"<p><p>Adenosine, acting on adenosine A(2A) receptors (A2ARs), regulates addictive processes induced by drugs of abuse. This study investigates the role of A(2A) adenosine receptors in neurochemical and behavioral responses to an acute cocaine challenge. Changes in the extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) of mice lacking A(2A) adenosine receptors and wild type (WT) littermates after an acute cocaine (20 mg/kg) administration were evaluated by in vivo microdialysis studies. Locomotor effects induced by cocaine were measured during the microdialysis procedure. Cocaine-evoked increases in extracellular DA were not sustained in mice lacking A(2A) Rs in comparison with wild-type mice (P < 0.05). Cocaine administration significantly increased ambulatory activity in both genotypes. However, overall locomotor activity was further increased, whereas rest and small local movement measures were significantly attenuated in the A(2A) R knockout mice compared with WT littermates (P < 0.05). Our findings support an important role for adenosine A(2A) R in modulating the acute effects of cocaine, as demonstrated by the decrease in cocaine-evoked dopaminergic transmission in the NAc. Furthermore, the results support an important antagonistic role of A(2A) R in vivo in regulating psychostimulant-induced hyperlocomotion.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"383-90"},"PeriodicalIF":2.3,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39966875","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":"Adolescent female rats exhibiting activity-based anorexia express elevated levels of GABA(A) receptor α4 and δ subunits at the plasma membrane of hippocampal CA1 spines.","authors":"Chiye Aoki, Nicole Sabaliauskas, Tara Chowdhury, Jung-Yun Min, Anna Rita Colacino, Kevin Laurino, Nicole C Barbarich-Marsteller","doi":"10.1002/syn.21528","DOIUrl":"10.1002/syn.21528","url":null,"abstract":"<p><p>Activity-based anorexia (ABA) is an animal model for anorexia nervosa that has revealed genetic links to anxiety traits and neurochemical characteristics within the hypothalamus. However, few studies have used this animal model to investigate the biological basis for vulnerability of pubertal and adolescent females to ABA, even though the great majority of the anorexia nervosa cases are females exhibiting the first symptoms during puberty. GABAergic inhibition of the hippocampus strongly regulates anxiety as well as plasticity throughout life. We recently showed that the hippocampal CA1 of female mice undergo a dramatic change at puberty onset--from expressing virtually none of the nonsynaptic α4βδ GABA(A) receptors (GABARs) prepubertally to expressing these GABARs at ~7% of the CA1 dendritic spine membranes at puberty onset. Furthermore, we showed that this change underlies the enhanced modulation of anxiety, neuronal excitability, and NMDA receptor-dependent synaptic plasticity in the hippocampus by the stress neurosteroid, THP (3α-OH-5α[β]-pregnan-20-one or [allo]pregnanolone). Here, we used quantitative electron microscopy to determine whether ABA induction in female rats during adolescence also elevates the expression of α4 and δ subunits of α4βδ GABARs, as was observed at puberty onset for mice. Our analysis revealed that rats also exhibit a rise of α4 and δ subunits of α4βδ GABARs at puberty onset, in that these subunits are detectable at ~6% of the dendritic spine membranes of CA1 pyramidal cells at puberty onset (postnatal day 32-36; P32-36) but this drops to about 2% by P40-P44. The levels of α4 and δ subunits at the CA1 spines remained low following exposure of females to either of the two environmental factors needed to generate ABA--food restriction and access to a running wheel for 4 days--from P40 to P44. This pattern contrasted greatly from those of ABA animals, for which the two environmental factors were combined. Within the hippocampus of ABA animals, 12% of the spine profiles were labeled for α4, reflecting a sixfold increase, relative to hippocampi of age-matched (P44) control females (p < 0.005). Concurrently, 7% of the spine profiles were labeled for δ, reflecting a 130% increase from the control values of 3% (p = 0.01). No measurable change was detected for spine size. The observed magnitude of increase in the α4 and δ subunits at spines is sufficient to increase both tonic inhibition of hippocampus and anxiety during stress, thereby likely to exacerbate hyperactivity and weight loss.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"391-407"},"PeriodicalIF":0.0,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292704/pdf/nihms349036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39967345","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":"Involvement of the cGMP pathway in the osthole-facilitated glutamate release in rat hippocampal nerve endings.","authors":"Tzu Yu Lin,&nbsp;Cheng Wei Lu,&nbsp;Wei-Jan Huang,&nbsp;Su-Jane Wang","doi":"10.1002/syn.21505","DOIUrl":"https://doi.org/10.1002/syn.21505","url":null,"abstract":"<p><p>Osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson, has previously been shown to have the capacity to increase depolarization-evoked glutamate release in rat hippocampal nerve terminals. As cGMP-dependent signaling cascade has been found to modulate glutamate release at the presynaptic level, the aim of this study was to further examine the role of cGMP signaling pathway in the regulation of osthole on glutamate release in hippocampal synaptosomes. Results showed that osthole dose-dependently increased intrasynaptosomal cGMP levels. The elevation of cGMP levels by osthole was prevented by the phosphodiesterase 5 inhibitor sildenafil but was insensitive to the guanylyl cyclase inhibitor ODQ. In addition, osthole-induced facilitation of 4-aminopyridine (4-AP)-evoked glutamate release was completely prevented by the cGMP-dependent protein kinase (PKG) inhibitors, KT5823, and Rp-8-Br-PET-cGMPS. Direct activation of PKG with 8-Br-cGMP or 8-pCPT-cGMP also occluded the osthole-mediated facilitation of 4-AP-evoked glutamate release. Furthermore, sildenafil exhibited a dose-dependent facilitation of 4-AP-evoked release of glutamate and occluded the effect of osthole on the 4-AP-evoked glutamate release. Collectively, our findings suggest that osthole-mediated facilitation of glutamate release involves the activation of cGMP/PKG-dependent pathway.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"232-9"},"PeriodicalIF":2.3,"publicationDate":"2012-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40122623","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":"Inhibition of the serotonin transporter induces microglial activation and downregulation of dopaminergic neurons in the substantia nigra.","authors":"L MacGillivray,&nbsp;K B Reynolds,&nbsp;M Sickand,&nbsp;P I Rosebush,&nbsp;M F Mazurek","doi":"10.1002/syn.20954","DOIUrl":"https://doi.org/10.1002/syn.20954","url":null,"abstract":"<p><p>Drugs that selectively inhibit the serotonin transporter (SERT) are widely used in the treatment of depression and anxiety disorders. These agents are associated with a range of extrapyramidal syndromes such as akathisia, dystonia, dyskinesia and parkinsonism, suggesting an effect on dopaminergic transmission. We studied the time course of changes in dopaminergic neurons in the substantia nigra (SN) after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (N = 9) or mixed with citalopram 5 mg/kg/day (N = 27). Rats were sacrificed after 24 h, 7 days or 28 days of treatment. Sections of SN were processed for tyrosine hydroxylase (TH) immunohistochemistry. Citalopram induced a significant decrease in TH-positive cell counts at 24 h (44%), 7 days (38%) and 28 days (33%). No significant differences among the citalopram treatment groups were observed in the SN. To determine whether these changes would occur with other SERT inhibitors, we conducted a second experiment, this time with a 28 day course of fluoxetine. As was observed with citalopram, fluoxetine induced a significant 21% reduction of TH cell counts in the SN. Immunoblot analysis showed that fluoxetine also induced a 45% reduction of striatal TH. To investigate a possible role for the innate immune system in mediating these changes, we also studied the microglial marker OX42 after administration of fluoxetine and noted a significant 63% increase in the SN of fluoxtine-treated animals. These results indicate that SERT inhibition can activate microglia and alter the regulation of TH, the rate limiting enzyme for dopamine biosynthesis. These changes may play a role in mediating the extrapyramidal side effects associated with SERT inhibitors.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1166-72"},"PeriodicalIF":2.3,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20954","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40086127","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":"Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.","authors":"Noah B Gross,&nbsp;Patrick C Duncker,&nbsp;John F Marshall","doi":"10.1002/syn.20952","DOIUrl":"https://doi.org/10.1002/syn.20952","url":null,"abstract":"<p><p>Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1144-55"},"PeriodicalIF":2.3,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20952","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40086125","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":"Involvement of NMDA receptors in ryanodine receptor expression in dopaminergic neurons in the ventral tegmental area of mice with intermittent methamphetamine treatment.","authors":"Kazuhiro Kurokawa,&nbsp;Masahiro Shibasaki,&nbsp;Emi Kiyokage,&nbsp;Koji Mizuno,&nbsp;Kazunori Toida,&nbsp;Seitaro Ohkuma","doi":"10.1002/syn.20953","DOIUrl":"https://doi.org/10.1002/syn.20953","url":null,"abstract":"<p><p>Excitatory synapses on dopaminergic neurons of the ventral tegmental area (VTA) represent an important role in psychostimulant-induced rewarding effect. This study investigated the regulation of ryanodine receptor (RyR) and N-methyl-D-aspartate (NMDA) receptor expression in mice under intermittent methamphetamine (METH) treatment using a place preference procedure. RyR-1 and -2 significantly increased in the VTA of mice with METH-induced place preference, whereas RyR-3 showed no changes. In addition, the levels of NR1, NR2A, and NR2B subunits were increased in the VTA. The METH-induced place preference was inhibited by intracerebroventricular pretreatment with MK-801, a noncompetitive NMDA receptor antagonist, and ifenprodil, a selective NR2B subunit-containing NMDA receptor antagonist, in a dose-dependent manner. Under these conditions, the increase of RyR-1 and -2 in the VTA was significantly blocked by ifenprodil. The immunohistochemical analysis revealed the colocalization of RyR-1 and -2 with NR2B subunits in dopaminergic neurons in the mouse VTA. These findings suggest that RyRs could be involved in the development of METH-induced place preference and that NR2B subunit-containing NMDA receptors in mice showing METH-induced place preference play an important role in expression of RyRs.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1156-65"},"PeriodicalIF":2.3,"publicationDate":"2011-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20953","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40086126","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}