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GABAB Receptor

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
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
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
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
Shane D Hellyer, Sabine Albold, Taide Wang, Amy Ny 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 pharmacological tools and therapeutic agents. While many Class C GPCR allosteric modulators have undergone subtype selectivity screening, most assay paradigms have failed to perform rigorous pharmacological assessment. Utilizing mGlu5 as a representative Class C GPCR, we tested the hypothesis that allosteric modulator selectivity was based on cooperativity rather than affinity...
March 7, 2018: Molecular Pharmacology
Kiyoto Kanbara, Yoshinori Otsuki, Masahito Watanabe, Syunichi Yokoe, Yoshiaki Mori, Michio Asahi, Masashi Neo
BACKGROUND: High-grade chondrosarcoma, which has a high incidence of local recurrence and pulmonary metastasis despite surgical resection, is associated with poor prognosis. Therefore, new and effective adjuvant therapies are urgently required for this disease. Gamma-aminobutyric acid (GABA), which acts as a neurotrophic factor during nervous system development, is related to the proliferation and migration of certain cancer cells. The GABAergic system, which is composed of GABA, the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), and GABA receptors, has an important function in nerve growth and development of neural crest...
March 7, 2018: BMC Cancer
Bojana Kokinovic, Paolo Medini
Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known on the microcircuit changes underlying recovery, at which extent perilesional plasticity occurs at synaptic input vs. spike output level, and on the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extra- and intra-cellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke of neighboring forelimb area (fS1), suggesting that in normal conditions they originate via horizontal connections from neighboring fS1...
March 5, 2018: Journal of Physiology
Sima Dameni, Atousa Janzadeh, Mahmoud Yousefifard, Farinaz Nasirinezhad
BACKGROUND: and aim: Irisin is a new myokine that is secreted by myocytes during exercise, and plays a role in creating the beneficial effects of exercise on metabolism. Considering the benefits of exercise in reducing pain, this study was carried out to determine the probable effect of irisin on neuropathic pain in the chronic constriction injury (CCI) model in male rats. METHODS: To induce neuropathic pain CCI model was used. Animals were divided into groups of control, CCI, sham, CCI + vehicle, and CCI + irisin...
February 28, 2018: Journal of Chemical Neuroanatomy
Nurul H M Yusoff, Sharif M Mansor, Christian P Müller, Zurina Hassan
Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats...
February 27, 2018: Behavioural Brain Research
Ravi Naik, Heather Valentine, Robert F Dannals, Dean F Wong, Andrew G Horti
New GABAB agonists, fluoropyridyl ether analogues of baclofen, have been synthesized as potential PET radiotracers. The compound with highest inhibition binding affinity as well as greatest agonist response, ( R)-4-amino-3-(4-chloro-3-((2-fluoropyridin-4-yl)methoxy)phenyl)butanoic acid (1b), was radiolabeled with18 F with good radiochemical yield, high radiochemical purity, and high molar radioactivity. The regional brain distribution of the radiolabeled ( R)-4-amino-3-(4-chloro-3-((2-[18 F]fluoropyridin-4-yl)methoxy)phenyl)butanoic acid, [18 F]1b, was studied in CD-1 male mice...
March 9, 2018: ACS Chemical Neuroscience
Leniz F Nurullin, Evgeny E Nikolsky, Artem I Malomouzh
It is generally accepted that gamma-aminobutyric acid (GABA) is a signaling molecule abundant in central synapses. In a number of studies though, it has been shown that GABA signaling functions in the peripheral nervous system as well, in particular, in the synapses of sympathetic ganglia. However, there exists no firm evidence on the presence of GABAergic signaling cascade in the intercellular junctions of the somatic nerve system. By the use of immunohistochemistry methods, in the synaptic area of cholinergic neuromuscular contact in rat diaphragm, we have detected glutamate decarboxylase, the enzyme involved in synthesis of GABA, molecules of GABA, and also GAT-2, a protein responsible for transmembrane transport of GABA...
February 26, 2018: Acta Histochemica
Kyungae Jo, Hyeon-Son Choi, SangDuck Jeon, Chang-Won Ahn, Hyung Joo Suh
The sleep-promoting effects of the water extract of Nelumbo nucifera seeds (NNE) were investigated in an invertebrate model. The effects of NNE on the subjective nighttime activity, sleep episodes, and sleep time were determined using Drosophila melanogaster and locomotor activity monitoring systems in basal and caffeine-induced arousal conditions. The movements of fruit flies were analyzed using the Noldus EthoVision-XT system, and the levels of neuromodulators were analyzed using HPLC. Expression of neuromodulator receptors was analyzed using real-time PCR...
2018: Biological & Pharmaceutical Bulletin
Katerina Koussoulas, Mathusi Swaminathan, Candice Fung, Joel C Bornstein, Jaime P P Foong
γ-Aminobutyric Acid (GABA) and its receptors, GABAA,B,C , are expressed in several locations along the gastrointestinal tract. Nevertheless, a role for GABA in enteric synaptic transmission remains elusive. In this study, we characterized the expression and function of GABA in the myenteric plexus of the mouse ileum. About 8% of all myenteric neurons were found to be GABA-immunoreactive (GABA+) including some Calretinin+ and some neuronal nitric oxide synthase (nNOS+) neurons. We used Wnt1-Cre;R26R-GCaMP3 mice, which express a genetically encoded fluorescent calcium indicator in all enteric neurons and glia...
2018: Frontiers in Physiology
Heather Nichol, Bénédicte Amilhon, Frédéric Manseau, Saishree Badrinarayanan, Sylvain Williams
The nicotinic acetylcholine receptor alpha2 subunit (Chrna2) is a specific marker for oriens lacunosum-moleculare (OLM) interneurons in the dorsal CA1 region of the hippocampus. It was recently shown using a Chrna2-cre mice line that OLM interneurons can modulate entorhinal cortex and CA3 inputs and may therefore have an important role in gating, encoding, and recall of memory. In this study, we have used a combination of electrophysiology and optogenetics using Chrna2-cre mice to determine the role of Chrna2 interneurons in the subiculum area, the main output region of the hippocampus...
2018: Frontiers in Cellular Neuroscience
Anthony Park, Olivia Uddin, Ying Li, Radi Masri, Asaf Keller
Pain after spinal cord injury (SCI-Pain) is one of the most debilitating sequelae of SCI, characterized as relentless, excruciating pain that is largely refractory to treatments. While it is generally agreed that SCI-Pain results from maladaptive plasticity in the pain processing pathway that includes the spinothalamic tract and somatosensory thalamus, the specific mechanisms underlying the development and maintenance of such pain are yet unclear. However, accumulating evidence suggests that SCI-Pain may be causally related to abnormal thalamic disinhibition, leading to hyperactivity in the posterior thalamic nucleus (PO), a higher order nucleus involved in somatosensory and pain processing...
February 23, 2018: Journal of Pain: Official Journal of the American Pain Society
Genane Loheswaran, Mera S Barr, Reza Zomorrodi, Tarek K Rajji, Daniel M Blumberger, Bernard Le Foll, Zafiris J Daskalakis
Alcohol is thought to exert its effect by acting on gamma-aminobutyric (GABA) inhibitory neurotransmission. The N100, the negative peak on electroencephalography (EEG) that occurs approximately 100 ms following the transcranial magnetic stimulation (TMS) pulse, is believed to represent GABAB receptor mediated neurotransmission. However, no studies have examined the effect of alcohol on the N100 response to TMS stimulation of the dorsolateral prefrontal cortex (DLPFC). In the present study, we aimed to explore the effect of alcohol on the DLPFC TMS-evoked N100 response...
February 21, 2018: Scientific Reports
Leah B Gerrard, Malinda L S Tantirigama, John M Bekkers
The piriform cortex (PC), like other cortical regions, normally operates in a state of dynamic equilibrium between excitation and inhibition. Here we examined the roles played by pre- and postsynaptic GABAB receptors in maintaining this equilibrium in the PC. Using whole-cell recordings in brain slices from the anterior PC of mice, we found that synaptic activation of postsynaptic GABAB receptors hyperpolarized the two major classes of layer 2 principal neurons and reduced the intrinsic electrical excitability of these neurons...
2018: Frontiers in Cellular Neuroscience
Phillip L W Colmers, Jaideep S Bains
Corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are integratory hubs that regulate the endocrine response to stress. GABA inputs provide a basal inhibitory tone that constrains this system and circulating glucocorticoids (CORT) are important feedback controllers of CRH output. Surprisingly little is known about the direct effects of CORT on GABA synapses in PVN. Here we used whole-cell patch clamp recordings from CRH neurons in mouse hypothalamic brain slices to examine the effects of CORT on synaptic and extrasynaptic GABA signalling...
February 8, 2018: Journal of Physiology
Alessandra Porcu, Miriam Melis, Rostislav Turecek, Celine Ullrich, Ignazia Mocci, Bernhard Bettler, Gian Luigi Gessa, M Paola Castelli
Rimonabant is a potent and selective cannabinoid CB1 receptor antagonist widely used in animal and clinical studies. Besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at CB1 receptors. The mechanism underpinning this activity is unclear. Here we show that micromolar concentrations of rimonabant inhibited Gαi/o-type G proteins, resulting in a receptor-independent block of G protein signaling. Accordingly, rimonabant decreased basal and agonist stimulated [35S]GTPγS binding to cortical membranes of CB1- and GABAB-receptor KO mice and Chinese Hamster Ovary (CHO) cell membranes stably transfected with GABAB or D2 dopamine receptors...
January 27, 2018: Neuropharmacology
L Wang, M Kloc, E Maher, A Erisir, A Maffei
Fast inhibitory GABAergic transmission plays a fundamental role in neural circuits. Current theories of cortical function assume that fast GABAergic inhibition acts via GABAA receptors on postsynaptic neurons, while presynaptic effects of GABA depend on GABAB receptor activation. Manipulations of GABAA receptor activity in vivo produced different effects on cortical function, which were generally ascribed to the mode of action of a drug, more than its site of action. Here we show that in rodent primary visual cortex, α4-containing GABAA receptors can be located on subsets of glutamatergic and GABAergic presynaptic terminals and decrease synaptic transmission...
January 24, 2018: Cerebral Cortex
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