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GABAB Receptor

Quratulane Gillani, Muhammad Ali, Furhan Iqbal
Interleukin (IL) 6 and 18 plays an important role in inflammatory response following hypoxia ischemia encephalopathy (HIE). Present study was designed to demonstrate the effect of two GABAB receptor antagonists (CGP 35348 and 55845), respectively, on the serum IL6 and IL 18 concentrations in albino mice. Albino mice pups (of both genders) were subjected to Murine model of hypoxia-ischemia encephalopathy on postnatal day 10 (right common carotid artery was ligated followed by 8% hypoxia for 25 minutes). After neonatal brain damage and following weaning, mice were divided in three groups, in gender specific manner, and fed on normal rodent diet till they were 13 week old...
September 2016: Pakistan Journal of Pharmaceutical Sciences
Flurin Cathomas, Hannes Sigrist, Luca Schmid, Erich Seifritz, Martin Gassmann, Bernhard Bettler, Christopher R Pryce
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABAB receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABAB receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12(-/-)) exhibit increased auditory fear learning and that Kctd12(+/-) mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons...
October 4, 2016: Behavioural Brain Research
Kyuhyun Choi, Youngin Lee, Changwoo Lee, Seokheon Hong, Soonje Lee, Shin Jung Kang, Ki Soon Shin
The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (γ -aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner...
October 5, 2016: Scientific Reports
Martijn M Selten, Francisca Meyer, Wei Ba, Astrid Vallès, Dorien A Maas, Moritz Negwer, Vivian D Eijsink, Ruben W M van Vugt, Josephus A van Hulten, Nick H M van Bakel, Joey Roosen, Robert J van der Linden, Dirk Schubert, Michel M M Verheij, Nael Nadif Kasri, Gerard J M Martens
Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats...
September 30, 2016: Scientific Reports
M Zhang, H J Hao, L P Liu, H H Zhang, Y Y Zhou
Autoimmune encephalitis with GABAB receptor antibodies has been rarely reported. Two cases of GABAB receptor antibodies encephalitis were presented here.Epilepsy was the onset symptom, followed by declined consciousness and frequent seizures. Fever was presented in the whole course of the disease. Myorhythmia of the two hands and pilomotor seizures were shown in the later course of the disease. No specificity was demonstrated in electroencephalograms and magnetic resonance imaging. Sensitive response was shown to the first-line immunotherapy...
October 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Wanhong Zuo, Liwei Wang, Lixin Chen, Krešimir Krnjević, Rao Fu, Xia Feng, Wen He, Seungwoo Kang, Avi Shah, Alex Bekker, Jiang-Hong Ye
Ethanol's aversive property may limit it's use, but the underlying mechanisms are no well-understood. Emerging evidence suggests a critical role for the lateral habenula (LHb) in the aversive response to various drugs, including ethanol. We previously showed that ethanol enhances glutamatergic transmission and stimulates LHb neurons. GABAergic transmission, a major target of ethanol in many brain regions, also tightly regulates LHb activity. This study assessed the action of ethanol on LHb GABAergic transmission in rat brain slices...
September 25, 2016: Neuropharmacology
Anne Lingford-Hughes, Yash Patel, Owen Bowden-Jones, Mike J Crawford, Paul I Dargan, Fabiana Gordon, Steve Parrott, Tim Weaver, David M Wood
BACKGROUND: GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include 'G' and 'liquid ecstasy'. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to 'come down' after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %...
September 27, 2016: Trials
Masoumeh Nazari, Alireza Komaki, Iraj Salehi, Abdolrahman Sarihi, Siamak Shahidi, Hamidreza Komaki, Ahmad Gangi
Long-term potentiation (LTP), a form of synaptic plasticity, is considered to be a critical cellular mechanism that underlies learning and memory. Cannabinoid CB1 and metabotropic GABAB receptors display similar pharmacological effects and co-localize in certain brain regions. In this study, we examined the effects of co-administration of the CB1 and GABAB antagonists AM251 and baclofen, respectively, on LTP induction in the rat dentate gyrus (DG). Male Wistar rats were anesthetized with urethane. A stimulating electrode was placed in the lateral perforant path (PP), and a bipolar recording electrode was inserted into the DG until maximal field excitatory postsynaptic potentials (fEPSPs) were observed...
September 20, 2016: Brain Research
Stylianos Kouvaros, Costas Papatheodoropoulos
The hippocampal synapses display a conspicuous ability for long-term plasticity, which is thought to contribute to learning and memory. Previous research has shown that long-term potentiation (LTP) greatly differs between the dorsal (DH) and ventral (VH) CA1 hippocampal synapses when induced by high-frequency stimulation. In this study, using rat hippocampal slices and more physiologically relevant activity patterns based on the frequency of the theta rhythm (i.e., theta-burst stimulation, TBS) we found that the DH compared with the VH displayed a higher ability for induction and stability of NMDA receptor-dependent LTP of the field excitatory postsynaptic potential...
September 20, 2016: Hippocampus
Porfirio Gómora-Arrati, Guadalupe Dominguez, Anders Ågmo
We studied the participation of GABA neurotransmission in the medial preoptic area (MPOA) in the onset of the pup retrieval response and nest building. Pregnant female rats were implanted with bilateral cannulae in the MPOA on 12 day of pregnancy, and on day 16 the females were hysterectomized-ovariectomized and given 200 μg/kg of estradiol benzoate. Two days later the females received one of the following intracerebral drug treatments: The GABAB agonist baclofen, 200 ng; the GABAB antagonist phaclofen, 1 μg; the GABAA antagonist bicuculline, 60 ng; physiological saline...
September 15, 2016: Journal of Neuroendocrinology
M Schou, S G Sæther, K Borowski, B Teegen, D Kondziella, W Stoecker, A Vaaler, S K Reitan
BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care...
September 9, 2016: Psychological Medicine
Francis M Rotella, Kerstin Olsson, Nancy Martinez, Alexandra Mordo, Ilanna Kohen, Alon Aminov, Jeremy Pagirsky, Alice Yu, Vishal Vig, Richard J Bodnar
Rats display conditioned flavor preferences (CFP) for fats. Previous studies demonstrated that whereas expression of an already-acquired corn oil (CO)-CFP was mildly reduced by dopamine (DA) D1, DA D2, NMDA or opioid receptor antagonists, the acquisition or learning of CO-CFP was eliminated by NMDA antagonists, and significantly reduced by DA D1 and D2, but not opioid antagonists. Previous studies of fructose-CFP demonstrated that muscarinic (scopolamine) and nicotinic (mecamylamine) cholinergic receptor antagonists and GABAB (baclofen) receptor agonism reduced the expression of this acquired response, and that scopolamine, but not mecamylamine or baclofen eliminated the acquisition or learning of this response...
September 4, 2016: Pharmacology, Biochemistry, and Behavior
Alessandra Porcu, Carla Lobina, Daniela Giunta, Maurizio Solinas, Claudia Mugnaini, M Paola Castelli
Positive allosteric modulators (PAMs) of the GABAB receptor have emerged as a novel approach to the pharmacological manipulation of the GABAB receptor, enhancing the effects of receptor agonists with few side effects. Here, we identified N-cyclohexyl-4-methoxy-6-(4-(trifluoromethyl)phenyl)pyrimidin-2-amine (SSD114) as a new compound with activity as a GABAB PAM in in vitro and in vivo assays. SSD114 potentiated GABA-stimulated [(35)S]GTPγS binding to native GABAB receptors, whereas it had no effect when used alone...
August 27, 2016: European Journal of Pharmacology
L M DePoy, A G Allen, S L Gourley
Adolescent cocaine use increases the likelihood of drug abuse and addiction in adulthood, and etiological factors may include a cocaine-induced bias towards so-called 'reward-seeking' habits. To determine whether adolescent cocaine exposure indeed impacts decision-making strategies in adulthood, we trained adolescent mice to orally self-administer cocaine. In adulthood, males with a history of escalating self-administration developed a bias towards habit-based behaviors. In contrast, escalating females did not develop habit biases; rather, low response rates were associated with later behavioral inflexibility, independent of cocaine dose...
2016: Translational Psychiatry
Khaled Zemoura, Claudia Trümpler, Dietmar Benke
GABAB receptors are heterodimeric G protein-coupled receptors, which control neuronal excitability by mediating prolonged inhibition. The magnitude of GABAB receptor-mediated inhibition essentially depends on the amount of receptors in the plasma membrane. However, the factors regulating cell surface expression of GABAB receptors are poorly characterized. Cell surface GABAB receptors are constitutively internalized and either recycled to the plasma membrane or degraded in lysosomes. The signal that sorts GABAB receptors to lysosomes is currently unknown...
August 29, 2016: Journal of Biological Chemistry
Libor Ustohal, Michaela Mayerova, Veronika Hublova, Hana Prikrylova Kucerova, Eva Ceskova, Tomas Kasparek
OBJECTIVES: Schizophrenia is accompanied by impaired cortical inhibition, as measured by several markers including the cortical silent period (CSP). It is thought that CSP measures gamma-aminobutyric acid receptors B (GABAB) mediated inhibitory activity. But the mutual roles of schizophrenia as a disease and the drugs used for the treatment of psychosis on GABA mediated neurotransmission are not clear. METHODS: We recruited 13 drug-naive patients with first-episode schizophrenia...
August 15, 2016: Journal of Psychopharmacology
Timothy Fung, Khalid A Asseri, Yahya I Asiri, Richard A Wall, Stephan K W Schwarz, Ernest Puil, Bernard A MacLeod
R-isovaline is a non-proteinogenic amino acid which produces analgesia in a range of nociceptive assays. Mediation of this effect by metabotropic receptors for γ-aminobutyric acid (GABA) and glutamate, demonstrated by previous work, may depend on the type of tissue or receptor system. The objective of this study was to assess the activity of R-isovaline acting at GABAB and group II metabotropic glutamate receptors in guinea pig ileum, which is known to exhibit well-defined responses to GABAB agonists such as baclofen...
August 10, 2016: European Journal of Pharmacology
Yun Lu, Chang-Jun Li, Cheng Chen, Pan Luo, Mei Zhou, Cai Li, Xu-Lin Xu, Qing Lu, Zhi He, Lian-Jun Guo
Anxiety is an affective disorder that is commonly observed after irreversible brain damage induced by cerebral ischemia and can delay the physical and cognitive recovery, which affects the quality of life of both the patient and family members. However, anxiety after ischemia has received less attention, and mechanisms underlying anxiety-like behaviours induced by chronic cerebral ischemia are under-investigated. In the present study, the chronic cerebral hypoperfusion model was established by the permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) in rats, and anxiety-related behaviours were evaluated...
November 2016: Neuropharmacology
Camille Mazo, Gabriel Lepousez, Antoine Nissant, Matthew T Valley, Pierre-Marie Lledo
UNLABELLED: Sensory perception emerges from the confluence of sensory inputs that encode the composition of external environment and top-down feedback that conveys information from higher brain centers. In olfaction, sensory input activity is initially processed in the olfactory bulb (OB), serving as the first central relay before being transferred to the olfactory cortex. In addition, the OB receives dense connectivity from feedback projections, so the OB has the capacity to implement a wide array of sensory neuronal computation...
August 10, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Saad Hannan, Kim Gerrow, Antoine Triller, Trevor G Smart
Here, we uncover a mechanism for regulating the number of active presynaptic GABAB receptors (GABABRs) at nerve terminals, an important determinant of neurotransmitter release. We find that GABABRs gain access to axon terminals by lateral diffusion in the membrane. Their relative accumulation is dependent upon agonist activation and the presence of the two distinct sushi domains that are found only in alternatively spliced GABABR1a subunits. Following brief activation of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing accumulation at presynaptic terminals in a Ca(2+)-dependent manner that involves phosphorylation of GABABR2 subunits at Ser783...
August 16, 2016: Cell Reports
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