Addiction Biology Unit – Publications

@article{Galaj:2021aa,

title = {Beta-caryophyllene inhibits cocaine addiction-related behavior by activation of PPARαand PPARγ: repurposing a FDA-approved food additive for cocaine use disorder},

author = {Ewa Galaj and Guo-Hua Bi and Allamar Moore and Kai Chen and Yi He and Eliot Gardner and Zheng-Xiong Xi},

url = {https://pubmed.ncbi.nlm.nih.gov/33069159/},

doi = {10.1038/s41386-020-00885-4},

isbn = {1740-634X},

year  = {2021},

date = {2021-01-01},

journal = {Neuropsychopharmacology},

volume = {46},

number = {4},

pages = {860--870},

abstract = {Cocaine abuse continues to be a serious health problem worldwide. Despite intense research, there is still no FDA-approved medication to treat cocaine use disorder (CUD). In this report, we explored the potential utility of beta-caryophyllene (BCP), an FDA-approved food additive for the treatment of CUD. We found that BCP, when administered intraperitoneally or intragastrically, dose-dependently attenuated cocaine self-administration, cocaine-conditioned place preference, and cocaine-primed reinstatement of drug seeking in rats. In contrast, BCP failed to alter food self-administration or cocaine-induced hyperactivity. It also failed to maintain self-administration in a drug substitution test, suggesting that BCP has no abuse potential. BCP was previously reported to be a selective CB2 receptor agonist. Unexpectedly, pharmacological blockade or genetic deletion of CB1, CB2, or GPR55 receptors in gene-knockout mice failed to alter BCP's action against cocaine self-administration, suggesting the involvement of non-CB1, non-CB2, and non-GPR55 receptor mechanisms. Furthermore, pharmacological blockade of μopioid receptor or Toll-like receptors complex failed to alter, while blockade of peroxisome proliferator-activated receptors (PPARα, PPARγ) reversed BCP-induced reduction in cocaine self-administration, suggesting the involvement of PPARαand PPARγin BCP's action. Finally, we used electrical and optogenetic intracranial self-stimulation (eICSS, oICSS) paradigms to study the underlying neural substrate mechanisms. We found that BCP is more effective in attenuation of cocaine-enhanced oICSS than eICSS, the former driven by optical activation of midbrain dopamine neurons in DAT-cre mice. These findings indicate that BCP may be useful for the treatment of CUD, likely by stimulation of PPARαand PPARγin the mesolimbic system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{GALAJ2021173072,

title = {Progress in opioid reward research: From a canonical two-neuron hypothesis to two neural circuits},

author = {Ewa Galaj and Zheng-Xiong Xi},

url = {https://pubmed.ncbi.nlm.nih.gov/33227308/},

doi = {https://doi.org/10.1016/j.pbb.2020.173072},

issn = {0091-3057},

year  = {2021},

date = {2021-01-01},

journal = {Pharmacology Biochemistry and Behavior},

volume = {200},

pages = {173072},

abstract = {Opioid abuse and related overdose deaths continue to rise in the United States, contributing to the national opioid crisis in the USA. The neural mechanisms underlying opioid abuse and addiction are still not fully understood. This review discusses recent progress in basic research dissecting receptor mechanisms and circuitries underlying opioid reward and addiction. We first review the canonical GABA-dopamine neuron hypothesis that was upheld for half a century, followed by major findings challenging this hypothesis. We then focus on recent progress in research evaluating the role of the mesolimbic and nigrostriatal dopamine circuitries in opioid reward and relapse. Based on recent findings that activation of dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is equally rewarding and that GABA neurons in the rostromedial tegmental nucleus (RMTg) and the substantia nigra pars reticula (SNr) are rich in mu opioid receptors and directly synapse onto midbrain DA neurons, we proposed that the RTMg→VTA → ventrostriatal and SNr → SNc → dorsostriatal pathways may act as the two major neural substrates underlying opioid reward and abuse. Lastly, we discuss possible integrations of these two pathways during initial opioid use, development of opioid abuse and maintenance of compulsive opioid seeking.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SHEN2021173104,

title = {Deletion of VGLUT2 in midbrain dopamine neurons attenuates dopamine and glutamate responses to methamphetamine in mice},

author = {Hui Shen and Kai Chen and Rosa Anna M Marino and Ross A McDevitt and Zheng-Xiong Xi},

url = {https://pubmed.ncbi.nlm.nih.gov/33444596/},

doi = {https://doi.org/10.1016/j.pbb.2021.173104},

issn = {0091-3057},

year  = {2021},

date = {2021-01-01},

journal = {Pharmacology Biochemistry and Behavior},

volume = {202},

pages = {173104},

abstract = {Methamphetamine (METH) is a highly addictive psychostimulant. The continuous use of METH may lead to its abuse and neurotoxicity that have been associated with METH-induced increases in release of dopamine (DA) and glutamate in the brain. METH action in DA has been shown to be mediated by redistribution of DA from vesicles into cytoplasm via vesicular monoamine transporter 2 (VMAT2) and the subsequent reversal of membrane DA transporter (DAT), while little is known about the mechanisms underlying METH-induced glutamate release. Recent studies indicate that a subpopulation of midbrain DA neurons co-expresses VMAT2 and vesicular glutamate transporter 2 (VGLUT2). Therefore, we hypothesized that METH-induced glutamate release may in part originate from such a dual phenotype of DA neurons. To test this hypothesis, we used Cre-LoxP techniques to selectively delete VGLUT2 from midbrain DA neurons, and then examined nucleus accumbens (NAc) DA and glutamate responses to METH using in vivo brain microdialysis between DA-VGLUT2-KO mice and their VGLUT2-HET littermates. We found that selective deletion of VGLUT2 from DA neurons did not significantly alter basal levels of extracellular DA and glutamate, but attenuated METH-induced increases in extracellular levels of DA and glutamate. In addition, DA-VGLUT2-KO mice also displayed lower locomotor response to METH than VGLUT2-HET control mice. These findings, for the first time, suggest that cell-type specific VGLUT2 expression in DA neurons plays an important role in the behavioral and neurochemical effects of METH. Glutamate corelease from DA neurons may in part contributes to METH-induced increase in NAc glutamate release.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Galaj8853,

title = {Dissecting the Role of GABA Neurons in the VTA versus SNr in Opioid Reward},

author = {Ewa Galaj and Xiao Han and Hui Shen and Chloe J Jordan and Yi He and Bree Humburg and Guo-Hua Bi and Zheng-Xiong Xi},

url = {https://pubmed.ncbi.nlm.nih.gov/33046548/},

doi = {10.1523/JNEUROSCI.0988-20.2020},

issn = {0270-6474},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Neuroscience},

volume = {40},

number = {46},

pages = {8853--8869},

publisher = {Society for Neuroscience},

abstract = {Opioid reward has traditionally been thought to be mediated by GABA-induced disinhibition of dopamine (DA) neurons in the VTA. However, direct behavioral evidence supporting this hypothesis is still lacking. In this study, we found that the μ opioid receptor (MOR) gene, Oprm1, is highly expressed in GABA neurons, with ~50% of GABA neurons in the substantia nigra pars reticulata (SNr), ~30% in the VTA, and ~70% in the tail of the VTA (also called the rostromedial tegmental nucleus) in male rats. No Oprm1 mRNA was detected in midbrain DA neurons. We then found that optogenetic inhibition of VTA DA neurons reduced intravenous heroin self-administration, whereas activation of these neurons produced robust optical intracranial self-stimulation in DAT-Cre mice, supporting an important role of DA neurons in opioid reward. Unexpectedly, pharmacological blockade of MORs in the SNr was more effective than in the VTA in reducing heroin reward. Optogenetic activation of VTA GABA neurons caused place aversion and inhibited cocaine, but not heroin, self-administration, whereas optogenetic activation of SNr GABA neurons caused a robust increase in heroin self-administration with an extinction pattern, suggesting a compensatory response in drug intake due to reduced heroin reward. In addition, activation of SNr GABA neurons attenuated heroin-primed, but not cue-induced, reinstatement of drug-seeking behavior, whereas inhibition of SNr GABA neurons produced optical intracranial self-stimulation and place preference. Together, these findings suggest that MORs on GABA neurons in the SNr play more important roles in opioid reward and relapse than MORs on VTA GABA neurons.SIGNIFICANCE STATEMENT Opioid reward has long been believed to be mediated by inhibition of GABA interneurons in the VTA that subsequently leads to disinhibition of DA neurons. In this study, we found that more μ opioid receptors (MORs) are expressed in GABA neurons in the neighboring SNr than in the VTA, and that pharmacological blockade of MORs in the SNr is more effective in reducing heroin reward than blockade of MORs in the VTA. Furthermore, optogenetic activation of VTA GABA neurons inhibited cocaine, but not heroin, self-administration, whereas activation of SNr GABA neurons inhibited heroin reward and relapse. These findings suggest that opioid reward is more likely mediated by stimulation of MORs in GABA afferents from other brain regions than in VTA GABA neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{https://doi.org/10.1111/bph.14625,

title = {Cannabinoid CB1 and CB2 receptor mechanisms underlie cannabis reward and aversion in rats},

author = {Krista J Spiller and Guo-hua Bi and Yi He and Ewa Galaj and Eliot L Gardner and Zheng-Xiong Xi},

url = {https://pubmed.ncbi.nlm.nih.gov/30767215/},

doi = {https://doi.org/10.1111/bph.14625},

year  = {2019},

date = {2019-01-01},

journal = {British Journal of Pharmacology},

volume = {176},

number = {9},

pages = {1268-1281},

abstract = {Background and Purpose Endocannabinoids are critically involved in brain reward functions, mediated by activation of CB1 receptors, reflecting their high density in the brain. However, the recent discovery of CB2 receptors in the brain, particularly in the midbrain dopamine neurons, has challenged this view and inspired us to re-examine the roles of both CB1 and CB2 receptors in the effects of cannabis. Experimental Approach In the present study, we used the electrical intracranial self-stimulation paradigm to evaluate the effects of various cannabinoid drugs on brain reward in laboratory rats and the roles of CB1 and CB2 receptors activation in brain reward function(s). Key Results Two mixed CB1 / CB2 receptor agonists, Δ9-tetrahydrocannabinol (Δ9-THC) and WIN55,212-2, produced biphasic effects---mild enhancement of brain-stimulation reward (BSR) at low doses but inhibition at higher doses. Pretreatment with a CB1 receptor antagonist (AM251) attenuated the low dose-enhanced BSR, while a CB2 receptor antagonist (AM630) attenuated high dose-inhibited BSR. To confirm these opposing effects, rats were treated with selective CB1 and CB2 receptor agonists. These compounds produced significant BSR enhancement and inhibition, respectively. Conclusions and Implications CB1 receptor activation produced reinforcing effects, whereas CB2 receptor activation was aversive. The subjective effects of cannabis depend on the balance of these opposing effects. These findings not only explain previous conflicting results in animal models of addiction but also explain why cannabis can be either rewarding or aversive in humans, as expression of CB1 and CB2 receptors may differ in the brains of different subjects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{JORDAN2019208,

title = {Progress in brain cannabinoid CB2 receptor research: From genes to behavior},

author = {Chloe J Jordan and Zheng-Xiong Xi},

url = {https://pubmed.ncbi.nlm.nih.gov/30611802/},

doi = {https://doi.org/10.1016/j.neubiorev.2018.12.026},

issn = {0149-7634},

year  = {2019},

date = {2019-01-01},

journal = {Neuroscience & Biobehavioral Reviews},

volume = {98},

pages = {208-220},

abstract = {The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, but display species differences in gene and receptor structures, CB2R expression, and receptor responses to various CB2R ligands. CB2R transcripts also differ between the brain and spleen. In the brain, CB2A is the major transcript isoform, while CB2A and CB2B transcripts are present at higher levels in the spleen. These new findings regarding brain versus spleen CB2R isoforms may in part explain why early studies failed to detect brain CB2R gene expression. Here, we review evidence supporting the expression and function of brain CB2R from gene and receptor levels to cellular functioning, neural circuitry, and animal behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gao:2018aa,

title = {Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats.},

author = {Jun-Tao Gao and Chloe J Jordan and Guo-Hua Bi and Yi He and Hong-Ju Yang and Eliot L Gardner and Zheng-Xiong Xi},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30283001},

doi = {10.1038/s41386-018-0231-5},

issn = {1740-634X (Electronic); 0893-133X (Linking)},

year  = {2018},

date = {2018-12-01},

journal = {Neuropsychopharmacology},

volume = {43},

number = {13},

pages = {2615--2626},

address = {Addiction Biology Unit, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, 21224, USA.},

abstract = {Opioid abuse is a rapidly growing public health crisis in the USA. Despite extensive research in the past decades, little is known about the etiology of opioid addiction or the neurobiological risk factors that increase vulnerability to opioid use and abuse. Recent studies suggest that the type 2 metabotropic glutamate receptor (mGluR2) is critically involved in substance abuse and addiction. In the present study, we evaluated whether low-mGluR2 expression may represent a risk factor for the development of opioid abuse and addiction using transgenic mGluR2-knockout (mGluR2-KO) rats. Compared to wild-type controls, mGluR2-KO rats exhibited higher nucleus accumbens (NAc) dopamine (DA) and locomotor responses to heroin, higher heroin self-administration and heroin intake, more potent morphine-induced analgesia and more severe naloxone-precipitated withdrawal symptoms. In contrast, mGluR2-KO rats displayed lower motivation for heroin self-administration under high price progressive-ratio (PR) reinforcement conditions. Taken together, these findings suggest that mGluR2 may play an inhibitory role in opioid action, such that deletion of this receptor results in an increase in brain DA responses to heroin and in acute opioid reward and analgesia. Low-mGluR2 expression in the brain may therefore be a risk factor for the initial development of opioid abuse and addiction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Uhl:2018aa,

title = {Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist.},

author = {George R Uhl and Maria J Martinez and Paul Paik and Agnieszka Sulima and Guo-Hua Bi and Malliga R Iyer and Eliot Gardner and Kenner C Rice and Zheng-Xiong Xi},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30348770},

doi = {10.1073/pnas.1720446115},

issn = {1091-6490 (Electronic); 0027-8424 (Linking)},

year  = {2018},

date = {2018-10-22},

journal = {Proc Natl Acad Sci U S A},

address = {Neurology and Research Services, New Mexico VA Healthcare System, Albuquerque, NM 87108; George.Uhl@va.gov.},

abstract = {Receptor-type protein tyrosine phosphatase D (PTPRD) is a neuronal cell-adhesion molecule/synaptic specifier that has been implicated in addiction vulnerability and stimulant reward by human genomewide association and mouse cocaine-conditioned place-preference data. However, there have been no reports of effects of reduced expression on cocaine self-administration. There have been no reports of PTPRD targeting by any small molecule. There are no data about behavioral effects of any PTPRD ligand. We now report (i) robust effects of heterozygous PTPRD KO on cocaine self-administration (These data substantially extend prior conditioned place-preference data and add to the rationale for PTPRD as a target for addiction therapeutics.); (ii) identification of 7-butoxy illudalic acid analog (7-BIA) as a small molecule that targets PTPRD and inhibits its phosphatase with some specificity; (iii) lack of toxicity when 7-BIA is administered to mice acutely or with repeated dosing; (iv) reduced cocaine-conditioned place preference when 7-BIA is administered before conditioning sessions; and (v) reductions in well-established cocaine self-administration when 7-BIA is administered before a session (in WT, not PTPRD heterozygous KOs). These results add to support for PTPRD as a target for medications to combat cocaine use disorders. 7-BIA provides a lead compound for addiction therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Han:2017aa,

title = {CB1 Receptor Activation on VgluT2-Expressing Glutamatergic Neurons Underlies Delta(9)-Tetrahydrocannabinol (Delta(9)-THC)-Induced Aversive Effects in Mice.},

author = {Xiao Han and Yi He and Guo-Hua Bi and Hai-Ying Zhang and Rui Song and Qing-Rong Liu and Josephine M Egan and Eliot L Gardner and Jing Li and Zheng-Xiong Xi},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28951549},

doi = {10.1038/s41598-017-12399-z},

issn = {2045-2322 (Electronic); 2045-2322 (Linking)},

year  = {2017},

date = {2017-11-26},

journal = {Sci Rep},

volume = {7},

number = {1},

pages = {12315},

address = {Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, 21224, USA.},

abstract = {Cannabis can be rewarding or aversive. Cannabis reward is believed to be mediated by activation of cannabinoid CB1 receptors (CB1Rs) on GABAergic neurons that disinhibit dopaminergic neurons in the ventral tegmental area (VTA). However, little is known about the mechanisms underlying cannabis aversion in rodents. In the present study, CB1Rs are found not only on VTA GABAergic neurons, but also on VTA glutamatergic neurons that express vesicular glutamate transporter 2 (VgluT2). We then used Cre-Loxp transgenic technology to selectively delete CB1Rs in VgluT2-expressing glutamatergic neurons (VgluT2-CB1 (-/-)) and Cre-dependent viral vector to express light-sensitive channelrhodopsin-2 into VTA glutamatergic neurons. We found that photoactivation of VTA glutamatergic neurons produced robust intracranial self-stimulation (ICSS) behavior, which was dose-dependently blocked by DA receptor antagonists, but enhanced by cocaine. In contrast, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive component of cannabis, produced dose-dependent conditioned place aversion and a reduction in the above optical ICSS in VgluT2-cre control mice, but not in VgluT2-CB1 (-/-) mice. These findings suggest that activation of CB1Rs in VgluT2-expressing glutamate neurons produces aversive effects that might explain why cannabinoid is not rewarding in rodents and might also account for individual differences in the hedonic effects of cannabis in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yang:2017aa,

title = {Deletion of Type 2 Metabotropic Glutamate Receptor Decreases Sensitivity to Cocaine Reward in Rats.},

author = {Hong-Ju Yang and Hai-Ying Zhang and Guo-Hua Bi and Yi He and Jun-Tao Gao and Zheng-Xiong Xi},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28700935},

doi = {10.1016/j.celrep.2017.06.046},

issn = {2211-1247 (Electronic)},

year  = {2017},

date = {2017-07-11},

journal = {Cell Rep},

volume = {20},

number = {2},

pages = {319--332},

address = {Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.},

abstract = {Cocaine users show reduced expression of the metabotropic glutamate receptor (mGluR2), but it is not clear whether this is a predisposing trait for addiction or a consequence of drug exposure. In this study, we found that a nonsense mutation at the mGluR2 gene decreased mGluR2 expression and altered the seeking and taking of cocaine. mGluR2 mutant rats show reduced sensitivity to cocaine reward, requiring more cocaine to reach satiation when it was freely available and ceasing their drug-seeking behavior sooner than controls when the response requirement was increased. mGluR2 mutant rats also show a lower propensity to relapse after a period of cocaine abstinence, an effect associated with reduced cocaine-induced dopamine and glutamate overflow in the nucleus accumbens. These findings suggest that mGluR2 polymorphisms or reduced availability of mGluR2 might be risk factors for the initial development of cocaine use but could actually protect against addiction by reducing sensitivity to cocaine reward.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang:2016aa,

title = {T394A Mutation at the mu Opioid Receptor Blocks Opioid Tolerance and Increases Vulnerability to Heroin Self-Administration in Mice.},

author = {Xiao-Fei Wang and Elisabeth Barbier and Yi-Ting Chiu and Yi He and Jia Zhan and Guo-Hua Bi and Hai-Ying Zhang and Bo Feng and Lee-Yuan Liu-Chen and Jia Bei Wang and Zheng-Xiong Xi},

url = {https://www.ncbi.nlm.nih.gov/pubmed/?term=Wang%20XF%5BAuthor%5D&cauthor=true&cauthor_uid=27707973},

doi = {10.1523/JNEUROSCI.0603-16.2016},

issn = {1529-2401 (Electronic); 0270-6474 (Linking)},

year  = {2016},

date = {2016-07-11},

journal = {J Neurosci},

volume = {36},

number = {40},

pages = {10392--10403},

address = {Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.},

abstract = {The etiology and pathophysiology underlying opioid tolerance and dependence are still unknown. Because mu opioid receptor (MOR) plays an essential role in opioid action, many vulnerability-related studies have focused on single nucleotide polymorphisms of MOR, particularly on A118G. In this study, we found that a single-point mutation at the MOR T394 phosphorylation site could be another important susceptive factor in the development of opioid tolerance and dependence in mice. T394A mutation, in which a threonine at 394 was replaced by an alanine, did not alter agonist binding to MOR and opioid analgesia, but resulted in loss of etorphine-induced MOR internalization in spinal dorsal horn neurons and opioid analgesic tolerance induced by either morphine or etorphine. In addition, this mutation also caused an increase in intravenous heroin self-administration and in nucleus accumbens dopamine response to heroin. These findings suggest that T394 phosphorylation following MOR activation causes MOR internalization and desensitization, which subsequently contributes to the development of tolerance in both opioid analgesia and opioid reward. Accordingly, T394A mutation blocks opioid tolerance and leads to an increase in brain dopamine response to opioids and in opioid-taking behavior. Thus, the T394 may serve as a new drug target for modulating opioid tolerance and the development of opioid abuse and addiction. SIGNIFICANCE STATEMENT: The mechanisms underlying opioid tolerance and susceptibility to opioid addiction remain unclear. The present studies demonstrate that a single-point mutation at the T394 phosphorylation site in the C-terminal of mu opioid receptor (MOR) results in loss of opioid tolerance and enhanced vulnerability to heroin self-administration. These findings suggest that modulation of the MOR-T394 phosphorylation or dephosphorylation status may have therapeutic potential in management of pain, opioid tolerance, and opioid abuse and addiction. Accordingly, MOR-T394 mutation or polymorphisms could be a risk factor in developing opioid abuse and addiction and therefore be used as a new biomarker in prediction and prevention of opioid abuse and addiction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Xue2016,

title = {Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice.},

author = {Xue Xue and Jing-Yu Yang and Yi He and Li-Rong Wang and Ping Liu and Li-Sha Yu and Guo-Hua Bi and Ming-Ming Zhu and Yue-Yang Liu and Rong-Wu Xiang and Xiao-Ting Yang and Xin-Yu Fan and Xiao-Min Wang and Jia Qi and Hong-Jie Zhang and Tuo Wei and Wei Cui and Guang-Lu Ge and Zheng-Xiong Xi and Chun-Fu Wu and Xing-Jie Liang},

url = {http://www.ncbi.nlm.nih.gov/pubmed/26974957},

doi = {10.1038/nnano.2016.23},

issn = {1748-3395 (Electronic); 1748-3387 (Linking)},

year  = {2016},

date = {2016-07-01},

journal = {Nat Nanotechnol},

volume = {11},

number = {7},

pages = {613--620},

address = {CAS Center for Excellence in Nanoscience, Chinese Academy of Sciences and National Center for Nanoscience and Technology of China, Beijing 100190, China.},

abstract = {Methamphetamine (METH) abuse is a serious social and health problem worldwide. At present, there are no effective medications to treat METH addiction. Here, we report that aggregated single-walled carbon nanotubes (aSWNTs) significantly inhibited METH self-administration, METH-induced conditioned place preference and METH- or cue-induced relapse to drug-seeking behaviour in mice. The use of aSWNTs alone did not significantly alter the mesolimbic dopamine system, whereas pretreatment with aSWNTs attenuated METH-induced increases in extracellular dopamine in the ventral striatum. Electrochemical assays suggest that aSWNTs facilitated dopamine oxidation. In addition, aSWNTs attenuated METH-induced increases in tyrosine hydroxylase or synaptic protein expression. These findings suggest that aSWNTs may have therapeutic effects for treatment of METH addiction by oxidation of METH-enhanced extracellular dopamine in the striatum.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Stempel:2016aa,

title = {Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus.},

author = {Vanessa A Stempel and Alexander Stumpf and Hai-Ying Zhang and Tugba Ozdogan and Ulrike Pannasch and Anne-Kathrin Theis and David-Marian Otte and Alexandra Wojtalla and Ildiko Racz and Alexey Ponomarenko and Zheng-Xiong Xi and Andreas Zimmer and Dietmar Schmitz},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27133464},

doi = {10.1016/j.neuron.2016.03.034},

issn = {1097-4199 (Electronic); 0896-6273 (Linking)},

year  = {2016},

date = {2016-05-08},

journal = {Neuron},

volume = {90},

number = {4},

pages = {795--809},

address = {Neuroscience Research Center (NWFZ), 10117 Berlin, Germany. Electronic address: vstempel@mrc-lmb.cam.ac.uk.},

abstract = {Endocannabinoids (eCBs) exert major control over neuronal activity by activating cannabinoid receptors (CBRs). The functionality of the eCB system is primarily ascribed to the well-documented retrograde activation of presynaptic CB1Rs. We find that action potential-driven eCB release leads to a long-lasting membrane potential hyperpolarization in hippocampal principal cells that is independent of CB1Rs. The hyperpolarization, which is specific to CA3 and CA2 pyramidal cells (PCs), depends on the activation of neuronal CB2Rs, as shown by a combined pharmacogenetic and immunohistochemical approach. Upon activation, they modulate the activity of the sodium-bicarbonate co-transporter, leading to a hyperpolarization of the neuron. CB2R activation occurred in a purely self-regulatory manner, robustly altered the input/output function of CA3 PCs, and modulated gamma oscillations in vivo. To conclude, we describe a cell type-specific plasticity mechanism in the hippocampus that provides evidence for the neuronal expression of CB2Rs and emphasizes their importance in basic neuronal transmission.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}