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GABAB Receptor

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https://www.readbyqxmd.com/read/29759132/the-gamma-aminobutyric-acid-b-receptor-in-depression-and-reward
#1
REVIEW
Laura H Jacobson, Styliani Vlachou, David A Slattery, Xia Li, John F Cryan
The metabotropic gamma-aminobutyric acid B (GABAB ) receptor was the first described obligate G protein-coupled receptor heterodimer and continues to set the stage for discoveries in G protein-coupled receptor signaling complexity. In this review, dedicated to the life and work of Athina Markou, we explore the role of GABAB receptors in depression, reward, and the convergence of these domains in anhedonia, a shared symptom of major depressive disorder and withdrawal from drugs of abuse. GABAB receptor expression and function are enhanced by antidepressants and reduced in animal models of depression...
June 1, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29746088/structure-activity-studies-reveal-the-molecular-basis-for-gabab-receptor-mediated-inhibition-of-high-voltage-activated-calcium-channels-by-%C3%AE-conotoxin-vc1-1
#2
Mahsa Sadeghi, Bodil B Carstens, Brid P Callaghan, James T Daniel, Han Shen Tae, Tracey O'Donnell, Joel Castro, Stuart M Brierley, David J Adams, David J Craik, Richard J Clark
α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABAB receptors (GABABR). Therefore it is unclear whether activation of GABABR or inhibition of α9α10 nAChRs is the analgesic mechanism...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29742721/coexistence-of-lambert-eaton-myasthenic-syndrome-and-autoimmune-encephalitis-with-anti-crmp5-cv2-and-anti-gabab-receptor-antibodies-in-small-cell-lung-cancer-a-case-report
#3
Hongfang Li, Aimei Zhang, Yanlei Hao, Hongzhi Guan, Zhanyun Lv
RATIONALE: Autoimmune encephalitis and Lambert-Eaton myasthenic syndrome are classic paraneoplastic neurological conditions common in patients with small cell lung cancer. PATIENT CONCERNS: The patient complained of tiredness, fluctuating recent memory loss, and inability to find his home. His family members reported a change in character, irritability, and paranoia. One month later, the patient had 1 grand mal seizure lasting 5 minutes. DIAGNOSIS: The patient was diagnosed with limbic encephalitis combined with Lambert-Eaton myasthenic syndrome...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29722299/the-adjustment-of-%C3%AE-aminobutyric-acid-a-tonic-subunits-in-huntington-s-disease-from-transcription-to-translation-to-synaptic-levels-into-the-neostriatum
#4
REVIEW
Abraham Rosas-Arellano, Argel Estrada-Mondragón, Carola A Mantellero, Carlos Tejeda-Guzmán, Maite A Castro
γ-Aminobutyric acid (GABA), plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABAA and GABAB , the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6, β3, δ, or ρ1-3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29717222/paraneoplastic-limbic-encephalitis-associated-with-lung-cancer
#5
Kaini Shen, Yan Xu, Hongzhi Guan, Wei Zhong, Minjiang Chen, Jing Zhao, Longyun Li, Mengzhao Wang
Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in lung cancer patients. We retrospectively investigated the clinical characteristics, treatment responses, and prognoses in 16 PLE patients who were subsequently diagnosed with lung cancer. Fifteen patients initially presented with disturbance of consciousness, 13 with disorientation, and 12 with seizures. Thirteen patients had autoantibodies, including eight with gamma aminobutyric acid B receptor (GABAB R) antibodies and eight with Hu antibodies...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29704609/complex-learning-induced-modifications-in-synaptic-inhibition-mechanisms-and-functional-significance
#6
REVIEW
Iris Reuveni, Longnian Lin, Edi Barkai
Following training in a difficult olfactory-discrimination (OD) task rats acquire the capability to perform the task easily, with little effort. This new acquired skill, of 'learning how to learn' is termed 'rule learning'. At the single cell level, rule learning in manifested in long-term enhancement of intrinsic neuronal excitability of piriform cortex (PC) pyramidal neurons, and in excitatory synaptic connections between these neuros to maintained cortical stability, such long-lasting increase in excitability must be accompanied by paralleled increase in inhibitory processes that would prevent hyper-excitable activation...
April 25, 2018: Neuroscience
https://www.readbyqxmd.com/read/29703993/cortical-inhibitory-markers-of-lifetime-suicidal-behavior-in-depressed-adolescents
#7
Charles P Lewis, Paul A Nakonezny, Caren J Blacker, Jennifer L Vande Voort, John D Port, Gregory A Worrell, Hang Joon Jo, Zafiris J Daskalakis, Paul E Croarkin
Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and γ-aminobutyric acid (GABA) are dysregulated in suicidal individuals. This study utilized single- and paired-pulse transcranial magnetic stimulation (TMS) to assess excitatory and inhibitory cortical functioning in healthy control adolescents (n = 20), depressed adolescents without any history of suicidal behavior ("Depressed", n = 37), and depressed adolescents with lifetime history of suicidal behavior ("Depressed+SB", n = 17)...
March 14, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29667225/activation-of-central-gaba-b-receptors-offsets-the-cyclosporine-counteraction-of-endotoxic-cardiovascular-outcomes-in-conscious-rats
#8
Marwa Y Sallam, Sahar M El-Gowilly, Abdel-Galil A Abdel-Galil, Mahmoud M El-Mas
We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study we investigated whether the facilitation of central γ-amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS-CSA interaction was determined in the absence and presence of drugs that activate GABAA or GABAB receptors or elevate synaptic GABA levels in the central nervous system...
April 18, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29651507/efficacy-and-side-effects-of-baclofen-and-the-novel-gaba-b-receptor-positive-allosteric-modulator-cmppe-in-animal-models-for-alcohol-and-cocaine-addiction
#9
Valentina Vengeliene, Tatiane T Takahashi, Olga A Dravolina, Irina Belozertseva, Edwin Zvartau, Anton Y Bespalov, Rainer Spanagel
RATIONALE: Preclinical studies suggest that the GABAB receptor is a potential target for treatment of substance use disorders. However, recent clinical trials report adverse effects in patients treated with the GABAB receptor agonist baclofen and even question efficacy. How can the discrepancy between preclinical and clinical findings be explained? OBJECTIVE: To test efficacy and adverse effects of baclofen and the novel GABAB positive allosteric modulator (PAM) CMPPE in rat addiction models, which were developed in accordance with DSM...
April 12, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29614714/cloning-synthesis-and-functional-characterization-of-a-novel-%C3%AE-conotoxin-lt1-3
#10
Jinqin Chen, Li Liang, Huying Ning, Fengtao Cai, Zhuguo Liu, Longxiao Zhang, Liangyi Zhou, Qiuyun Dai
α-Conotoxins (α-CTxs) are small peptides composed of 11 to 20 amino acid residues with two disulfide bridges. Most of them potently and selectively target nicotinic acetylcholine receptor (nAChR) subtypes, and a few were found to inhibit the GABAB receptor (GABAB R)-coupled N-type calcium channels (Cav2.2). However, in all of α-CTxs targeting both receptors, the disulfide connectivity arrangement "C¹-C³, C²-C⁴" is present. In this work, a novel α4/7-CTx named Lt1.3 (GCCSHPACSGNNPYFC-NH₂) was cloned from the venom ducts of Conus litteratus ( C...
March 31, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29588966/pathogenic-potential-of-antibodies-to-the-gaba-b-receptor
#11
Anjan Nibber, Edward O Mann, Philippa Pettingill, Patrick Waters, Sarosh R Irani, Dimitri M Kullmann, Angela Vincent, Bethan Lang
GABAB receptor (GABAB R) autoantibodies have been detected in the serum of immunotherapy-responsive patients with autoimmune encephalitis. This study aimed to investigate the effect of immunoglobulin G (IgG) from a patient with GABAB R antibodies on primary neuronal cultures and acute slices of entorhinal cortex. Primary hippocampal neuronal cultures were incubated with serum immunoglobulin from patients with GABAB R or AMPA receptor (AMPAR) antibodies for up to 72 h to investigate their effect on receptor surface expression...
September 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29580154/inhibitory-g-i-o-coupled-receptors-in-somatosensory-neurons-potential-therapeutic-targets-for-novel-analgesics
#12
Yevgen Yudin, Tibor Rohacs
Primary sensory neurons in the dorsal root ganglia and trigeminal ganglia are responsible for sensing mechanical and thermal stimuli, as well as detecting tissue damage. These neurons express ion channels that respond to thermal, mechanical, or chemical cues, conduct action potentials, and mediate transmitter release. These neurons also express a large number of G-protein coupled receptors, which are major transducers for extracellular signaling molecules, and their activation usually modulates the primary transduction pathways...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29572837/cholecystokinin-selectively-activates-short-axon-cells-to-enhance-inhibition-of-olfactory-bulb-output-neurons
#13
Xiang Liu, Shaolin Liu
Neuropeptides including cholecystokinin (CCK) are important for many brain functions including sensory processing. CCK is predominantly present in a subpopulation of excitatory neurons and activation of CCK receptors is implicated in olfactory signal processing in the olfactory bulb (OB). However, cellular and circuit mechanisms underlying CCK actions in the OB remain elusive. Here we characterized CCK effects on synaptic inhibition of the principal OB output neurons mitral/tufted cells (MTCs) followed by mechanistic analyses at the circuit and cellular levels with the following findings...
March 23, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29572124/short-interval-and-long-interval-intracortical-inhibition-of-tms-evoked-eeg-potentials
#14
Isabella Premoli, Julia Király, Florian Müller-Dahlhaus, Carl M Zipser, Pierre Rossini, Christoph Zrenner, Ulf Ziemann, Paolo Belardinelli
BACKGROUND: Inhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2-3 ms (short-interval intracortical inhibition, SICI) or ∼100 ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively. OBJECTIVE/HYPOTHESIS: SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied...
March 15, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29567624/functional-inactivation-of-the-orbitofrontal-cortex-disrupts-context-induced-reinstatement-of-alcohol-seeking-in-rats
#15
Paula Cristina Bianchi, Paulo Eduardo Carneiro de Oliveira, Paola Palombo, Rodrigo Molini Leão, Hugo Cogo-Moreira, Cleopatra da Silva Planeta, Fábio Cardoso Cruz
BACKGROUND: The high rate of relapse to drug use remains a central challenge to treating drug addiction. In human and rat models of addiction, environmental stimuli in contexts associated with previous drug use can provoke a relapse of drug seeking. Pre-clinical studies have used the ABA renewal procedure to study context-induced reinstatement of drug seeking. In the current study, we studied the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to alcohol. METHODS: We trained male and female rats to self-administer alcohol in context A, extinguished drug-reinforced responding in a distinct context B, and assessed context-induced reinstatement in context A or B (control group)...
March 2, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29565038/gabaergic-inhibitory-neurons-as-therapeutic-targets-for-cognitive-impairment-in-schizophrenia
#16
REVIEW
Meng-Yi Xu, Albert H C Wong
Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing...
March 22, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29559911/vortioxetine-treatment-reverses-subchronic-pcp-treatment-induced-cognitive-impairments-a-potential-role-for-serotonin-receptor-mediated-regulation-of-gaba-neurotransmission
#17
Alan L Pehrson, Christian S Pedersen, Kirstine Sloth Tølbøl, Connie Sanchez
Major depressive disorder (MDD) is associated with cognitive impairments that may contribute to poor functional outcomes. Clinical data suggests that the multimodal antidepressant vortioxetine attenuates some cognitive impairments in MDD patients, but the mechanistic basis for these improvements is unclear. One theory suggests that vortioxetine improves cognition by suppressing γ-amino butyric acid (GABA)ergic neurotransmission, thereby increasing glutamatergic activation. Vortioxetine's effects on cognition, GABA and glutamate neurotransmission have been supported in separate experiments, but no empirical work has directly connected vortioxetine's cognitive effects to those on GABA and glutamate neurotransmission...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29559416/music-therapy-inhibits-morphine-seeking-behavior-via-gaba-receptor-and-attenuates-anxiety-like-behavior-induced-by-extinction-from-chronic-morphine-use
#18
Ki Jin Kim, Sang Nam Lee, Bong Hyo Lee
RATIONALE: Morphine is a representative pain killer. However, repeated use tends to induce addiction. Music therapy has been gaining interest as a useful type of therapy for neuropsychiatric diseases. OBJECTIVES: The present study examined whether Korean traditional music (KT) could suppress morphine-seeking behavior and anxiety-like behavior induced by extinction from chronic morphine use and additionally investigated a possible neuronal mechanism. MATERIAL & METHODS: Male Sprague-Dawley rats were trained to intravenously self-administer morphine hydrochloride (1...
March 17, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29531964/overexpression-of-channelrhodopsin-2-interferes-with-the-gabab-receptor-mediated-depression-of-gaba-release-from-the-somatostatin-containing-interneurons-of-the-prefrontal-cortex
#19
Lei Liu, Wataru Ito, Alexei Morozov
Region and cell-type restricted expression of light-activated ion channels is the indispensable tool to study properties of synapses in specific circuits and to monitor synaptic alterations by various stimuli including neuromodulators and behaviors, both ex vivo and in vivo . These analyses require the light-activated proteins or viral vectors for their delivery that do not interfere with the phenomenon under study. Here, we report a case of such interference in which the high-level expression of channelrhodopsin-2 introduced in the somatostatin-positive GABAergic neurons of the dorsomedial prefrontal cortex by an adeno-associated virus vector weakens the presynaptic GABAb receptor-mediated suppression of GABA release...
April 2018: Neurophotonics
https://www.readbyqxmd.com/read/29514854/-selective-class-c-g-protein-coupled-receptor-modulators-are-neutral-or-biased-mglu-5-allosteric-ligands
#20
Shane D Hellyer, Sabine Albold, Taide Wang, Amy N Y Chen, Lauren T May, Katie Leach, Karen J Gregory
Numerous positive and negative allosteric modulators (PAMs and NAMs) of class C G protein-coupled receptors (GPCRs) have been developed as valuable preclinical pharmacologic tools and therapeutic agents. Although many class C GPCR allosteric modulators have undergone subtype selectivity screening, most assay paradigms have failed to perform rigorous pharmacologic assessment. Using mGlu5 as a representative class C GPCR, we tested the hypothesis that allosteric modulator selectivity was based on cooperativity rather than affinity...
May 2018: Molecular Pharmacology
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