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Luara A Batista, Fabricio A Moreira
The endocannabinoid system has been implicated in the modulation of behaviors related to anxiety and panic disorders. Accordingly, facilitation of CB1 receptor signaling reduces the consequences of aversive stimuli in animal models. However, the role of the CB1 receptor in the effects of anxiolytic drugs has remained unclear. Here, we tested the hypothesis that the anxiolytic and panicolytic responses to systemic alprazolam injection and local 5-HT1A receptor activation in the dorsolateral periaqueductal gray (dlPAG) depend on CB1 receptor activation...
March 8, 2019: Neuroscience Letters
Marcos Ucha, David Roura-Martínez, Ana Contreras, Sheyla Pinto-Rivero, Javier Orihuel, Emilio Ambrosio, Alejandro Higuera-Matas
The orbitofrontal cortex (OFC) is a key brain region for decision-making, action control and impulsivity. Quite notably, previous research has identified a double dissociation regarding the role of this cortical territory in impulsive choice. While medial orbitofrontal lesions increase preference for a large but delayed reward, lateral orbitofrontal lesions have the opposite effect. However, there are no data regarding this anatomical dissociation in impulsive action. The neurochemical basis of impulsivity is still being elucidated, however, in recent years a role for the endocannabinoids and the related glutamatergic and GABAergic neurotransmitter systems has been suggested...
2019: Frontiers in Behavioral Neuroscience
Krista J Spiller, Guo-Hua Bi, Yi He, Ewa Galaj, Eliot L Gardner, Zheng-Xiong Xi
BACKGROUND AND PURPOSE: Endocannabinoids are critically involved in brain reward functions. This is generally believed to be mediated by activation of CB1 receptors, in large part due to their high density in the brain. However, the recent discovery of CB2 receptors (CB2 R) in the brain, particularly in midbrain dopamine neurons, has challenged this view and inspired us to re-examine the roles of both CB1 R and CB2 R in the effects of cannabis. EXPERIMENTAL APPROACH: In the present study, we used the electrical intracranial self-stimulation (ICSS) paradigm to evaluate the effects of various cannabinoid drugs on brain reward in laboratory rats, and the roles of CB1 R and CB2 R activation in brain reward function(s)...
February 14, 2019: British Journal of Pharmacology
Takayuki Myose, Atsunori Shirakawa, Keiichi Irie, Yuta Yamashita, Takafumi Nakano, Yumi Takase, Koichi Matsuo, Tomomitsu Satho, Ryota Tuchihashi, Junei Kinjo, Hiroyuki Tanaka, Satoshi Morimoto, Masahiko Funada, Kazunori Sano, Kenichi Mishima
Δ9 -Tetrahydrocannabinol (THC) is known to have various pharmacological effects mediated through activation of cannabinoid CB1 and CB2 receptors in rodents. In adult rats, 22- and 50-kHz ultrasonic vocalizations (USVs) serve as an effective communication system and as indicators of negative and positive states, respectively. The present study was performed to determine whether THC affects USVs in adult rats, and to determine the roles of cannabinoid receptors in these effects. THC (1, 3 mg/kg) was administered intraperitoneally to adult male Wistar rats 60 minutes before measurement of USVs...
February 8, 2019: Neuroscience Letters
Liane I F Moura, Cristina Lemos, Catherine Ledent, Eugénia Carvalho, Attila Köfalvi
Both endocannabinoids and insulin regulate peripheral and cerebral glucose homeostasis via convergent signaling pathways that are impacted by diabetes. Here we asked how glucose metabolism and important facets of insulin signaling are affected in the forebrain of cannabinoid CB1 receptor knockout mice (CB1 R-KO) and their wild-type (WT) littermates, seven weeks after the induction of insulinopenia/hyperglycemia (diabetes) with intraperitoneal streptozotocin injection. Sham-injected animals served as control...
February 2, 2019: Brain Research Bulletin
Roberto Colangeli, Roberto Di Maio, Massimo Pierucci, Gabriele Deidda, Maurizio Casarrubea, Giuseppe Di Giovanni
Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE)...
February 1, 2019: Neurobiology of Disease
Daniela da Fonseca Pacheco, Thiago Roberto Lima Romero, Igor Dimitri Gama Duarte
The participation of endocannabinoids in central and peripheral antinociception induced by several compounds has been shown by our group. In this study, we investigated the effect of endocannabinoids on the central antinociception induced by ketamine. The nociceptive threshold for thermal stimulation was measured using the tail-flick test in Swiss mice. The drugs were administered intracerebroventricularly. Probabilities less than 5% (p<0.05) were considered to be statistically significant (Two-way ANOVA/Bonferroni's test)...
February 1, 2019: Neuroscience Letters
Dragos Apostu, Ondine Lucaciu, Alexandru Mester, Horea Benea, Daniel Oltean-Dan, Florin Onisor, Mihaela Baciut, Simion Bran
Bone is a complex tissue of the with unique properties such as high strength and regeneration capabilities while carrying out multiple functions. Bone regeneration occurs both in physiological situations (bone turnover) and pathological situations (e.g. fractures), being performed by osteoblasts and osteoclasts. If this process is inadequate, fracture nonunion or aseptic loosening of implants occurs and requires a complex treatment. Exogenous factors are currently used to increase bone regeneration process when needed, such as bisphosphonates and vitamin D, but limitations do exist...
January 31, 2019: Drug Metabolism Reviews
Chen-Jie Shen, Di Zheng, Ke-Xin Li, Jian-Ming Yang, Hao-Qi Pan, Xiao-Dan Yu, Jia-Yu Fu, Yi Zhu, Qi-Xin Sun, Meng-Yu Tang, Ying Zhang, Peng Sun, Yi Xie, Shumin Duan, Hailan Hu, Xiao-Ming Li
In the version of this article originally published, there were several errors in Fig. 4. In Fig. 4a, the title read '3D repeated optical inhibition after CSDS.' It should have read '3-day repeated optical inhibition after CSDS.' In Fig. 4c, two labels that should have been aligned with the time axis appeared in the wrong place in the figure. The ticks labeled 'SI' and 'Fiber implant' should have also been labeled with '10' and '14,' respectively. Additionally, in Fig. 4j, a label that should have been aligned with the time axis appeared in the wrong place in the figure...
January 30, 2019: Nature Medicine
Eva Martínez-Pinilla, David Aguinaga, Gemma Navarro, Alberto J Rico, Julen Oyarzábal, Juan A Sánchez-Arias, José Luis Lanciego, Rafael Franco
Cannabinoid CB1 receptors (CB1 R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson's disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP+ , that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake MPP+ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death...
January 28, 2019: Molecular Neurobiology
Chen-Jie Shen, Di Zheng, Ke-Xin Li, Jian-Ming Yang, Hao-Qi Pan, Xiao-Dan Yu, Jia-Yu Fu, Yi Zhu, Qi-Xin Sun, Meng-Yu Tang, Ying Zhang, Peng Sun, Yi Xie, Shumin Duan, Hailan Hu, Xiao-Ming Li
Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world's population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular mechanisms through which BLA neurons modulate depressive behavior are largely uncharacterized. Here, in mice, we identified that BLA cholecystokinin (CCK) glutamatergic neurons mediated negative reinforcement via D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and that chronic social defeat selectively potentiated excitatory transmission of the CCKBLA -D2NAc circuit in susceptible mice via reduction of presynaptic cannabinoid type-1 receptor (CB1 R)...
January 14, 2019: Nature Medicine
Toshiyuki Kimura, Makiko Takaya, Noriyuki Usami, Kazuhito Watanabe, Ikuo Yamamoto
Purpose: ∆9 - Tetrahydrocannabinol (∆9 -THC) and cannabidiol (CBD), major psychoactive constituents of marijuana, induce potentiation of pentobarbital-induced sleep in mice. We have elucidated the mechanism of enhancement of the anesthetic effect of pentobarbital by cannabinoids. Methods: We carried out pharmacological experiment and cannabinoid1 (CB1 ) receptor binding assay using CB1 antagonists to clarify whether the CB1 receptor is involved in the synergism or not...
2019: Forensic Toxicology
Robert B Kargbo
No abstract text is available yet for this article.
December 13, 2018: ACS Medicinal Chemistry Letters
Astrid Pechmann, Sven Wellmann, Benjamin Stoecklin, Marcus Krüger, Barbara Zieger
INTRODUCTION: Primary blood coagulation and wound sealing are orchestrated by von Willebrand factor (VWF), a large multimeric glycoprotein. Upon release of arginine vasopressin (AVP), VWF containing high molecular weight multimers is secreted. By measuring copeptin, the C-terminal part of the AVP prohormone, we recently found strongly increased AVP levels in children with febrile seizures (FS) as compared to children with fever but without seizures. It is unknown if increased AVP levels in FS are of any biological function...
2019: PloS One
K R Trexler, M L Eckard, S G Kinsey
Recently, multiple compounds have been synthesized that target the allosteric binding site(s) of CB1. These CB1 positive allosteric modulators, may capture the benefits of cannabinoid receptor activation without unwanted psychoactive effects, such as sedation. For example, ZCZ011 blocks neuropathic pain, absent the catalepsy, sedation, and hypothermia caused by CB1 orthosteric modulators, including Δ9 -tetrahydrocannabinol (THC). The primary goal of the present study was to evaluate the potential of ZCZ011 to attenuate somatic signs of cannabinoid withdrawal in mice...
December 28, 2018: Pharmacology, Biochemistry, and Behavior
M C G Leite-Avalca, F T Staats, D Verona, P de Souza, M C Almeida, J E Silva-Santos, A R Zampronio
Sepsis is a life-threatening condition with high mortality rates that is caused by dysregulation of the host response to infection. We previously showed that treatment with the cannabinoid CB1 receptor antagonist rimonabant reduced mortality rates in animals with sepsis that was induced by cecal ligation and puncture (CLP). This improvement in the survival rate appeared to be related to an increase in arginine vasopressin (AVP) levels 12 h after CLP. The present study investigated the effects of rimonabant on organ dysfunction, hematologic parameters, and vascular reactivity in male Wistar rats with sepsis induced by CLP...
December 17, 2018: Inflammation
Jolanta Weresa, Anna Pędzińska-Betiuk, Rafał Kossakowski, Barbara Malinowska
BACKGROUND: Drugs targeting CB1 and CB2 receptors have been suggested to possess therapeutic benefit in cardiovascular disorders associated with elevated sympathetic tone. Limited data suggest cannabinoid ligands interact with postsynaptic β-adrenoceptors. The aim of this study was to examine the effects of CB1 and CB2 antagonists, AM251 and AM630, respectively, at functional cardiac β-adrenoceptors. METHODS: Experiments were carried out in isolated spontaneously beating right atria and paced left atria where inotropic and chronotropic increases were induced by isoprenaline and selective agonists of β1 and β2 -adrenergic receptors...
September 17, 2018: Pharmacological Reports: PR
Tatiana Lokot, Alexander Mehler, Olga Abramov
In this paper, we study the limit of compactness which is a graph index originally introduced for measuring structural characteristics of hypermedia. Applying compactness to large scale small-world graphs (Mehler, 2008) observed its limit behaviour to be equal 1. The striking question concerning this finding was whether this limit behaviour resulted from the specifics of small-world graphs or was simply an artefact. In this paper, we determine the necessary and sufficient conditions for any sequence of connected graphs resulting in a limit value of CB = 1 which can be generalized with some consideration for the case of disconnected graph classes (Theorem 3)...
2018: PloS One
N I Selivanov, A A Murashkina, R Kevorkyants, A V Emeline, D W Bahnemann
Two novel hybrid organic-inorganic perovskites, pyridinium lead tribromide and pyridinium lead triiodide, are prepared. Based on the XRD data, we find that the compounds are quasi-one-dimensional crystals of Pna21 symmetry. DFT calculations demonstrate that the valence band of the new compounds is comprised of the occupied p-orbitals of the halogen anions, while their conduction bands CB and CB + 1 are composed mainly of the unoccupied π-orbitals of the aromatic pyridinium rings. The computed DOS matches well with the recorded XPS spectra...
November 22, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Sheila Leone, Claudio Ferrante, Lucia Recinella, Annalisa Chiavaroli, Adriano Mollica, Csaba Tömböly, Azzurra Stefanucci, Marilisa Pia Dimmito, Szabolcs Dvorácskó, Vittore Verratti, Luciano De Petrocellis, Giustino Orlando, Luigi Brunetti
Palatability and variety of foods are major reasons for hedonic eating, and hence for obesity. Hemopressin, a hemoglobin α chain-derived peptide, plays antagonist/inverse agonist role on cannabinoid (CB)1 receptors, while RVD-hemopressin(α)[RVD-hp(α)], a N-terminally extended form of hemopressin, has been reported as an allosteric modulator of CB1 and CB2 receptors. We investigated the effects of 14 daily intraperitoneal injections of RVD-hp(α), in Sprague-Dawley rats fed a highly palatable cafeteria-style (CAF) diet (30% fat, 56% carbohydrate, 14% protein; 4...
December 2018: Neuropeptides
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