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https://www.readbyqxmd.com/read/28807483/the-potential-efficacy-of-gabab-antagonists-in-depression
#1
REVIEW
Robert C Alexander
Evidence for the potential utility of GABAB antagonists has been assembled from a variety of sources, including clinical experience with the GABAB agonist baclofen, murine genetic GABAB knock-outs, rodent studies of GABAB receptor expression and function following treatment with antidepressant therapies, animal models of depression, and some functional and post mortem data from human subjects. Definitive testing of GABAB antagonists in depression, however, still awaits the development of potent, selective and brain-penetrant compounds for human testing...
August 11, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28803835/receptor-distribution-studies
#2
REVIEW
Renzo Carletti, Stefano Tacconi, Manolo Mugnaini, Philip Gerrard
Receptor distribution studies have played a key role in the characterization of receptor systems (e.g. GABAB, NMDA (GluNRs), and Neurokinin 1) and in generating hypotheses to exploit these systems as potential therapeutic targets. Distribution studies can provide important information on the potential role of candidate receptors in normal physiology/disease and alert for possible adverse effects of targeting the receptors. Moreover, they can provide valuable information relating to quantitative target engagement (e...
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28801194/medial-septum-modulates-hippocampal-gamma-activity-and-prepulse-inhibition-in-an-n-methyl-d-aspartate-receptor-antagonist-model-of-schizophrenia
#3
L Stan Leung, Jingyi Ma
We reviewed the participation of the septohippocampal system in an animal model of schizophrenia that was acutely induced by systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist such as phencyclidine, MK-801 and ketamine. The NMDA receptor antagonist-induced model of schizophrenia is characterized by behavioral and electrophysiological disruptions, including a decrease in prepulse inhibition of the acoustic startle response (PPI), hyperlocomotion, decrease in gating of hippocampal auditory evoked potentials and robust increase in hippocampal gamma (30-100Hz) oscillations...
August 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28800869/the-role-of-ca3-gabab-receptors-on-anxiolytic-like-behaviors-and-avoidance-memory-deficit-induced-by-d-ap5-with-respect-to-ca-2-ions
#4
Shahram Zarrabian, Mohammad Nasehi, Maryam Farrahizadeh, Mohammad-Reza Zarrindast
Glutamatergic and GABAergic systems play key roles in the hippocampus and affect the pathogenesis of anxiety- and memory-related processes. Some investigations have assessed the role of balancing the function of these two systems in different areas of the central nervous system (CNS) as an approach to manage the related disorders. We investigated the anxiety and avoidance memory states using the test-retest protocol in the elevated plus maze to understand the role of GABAB receptors (GABABRs) in relation to the NMDA receptor blockade by D-AP5 (an NMDA receptor antagonist)...
August 8, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28795551/-gabab-paraneoplastic-encephalitis-about-a-clinical-case
#5
V Reiters, N Garzaniti, K Windhausen
The paraneoplastic limbic encephalitis is a rare disease. It is caused by the presence of autoantibodies creating an inflammatory reaction of the predominant brain parenchyma in the meso-temporal lobe and in other parts of the limbic system. Its presence requires looking for an underlying tumour. The management of this paraneoplastic syndrome includes an immunosuppressive therapy in addition to the treatment of the underlying tumour. However, the management of this disease is not yet standardized.
July 2017: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28789769/-autoimmune-encephalitis-presenting-with-drug-resistant-status-epilepticus
#6
Mette Nissen, Morten Blaabjerg
Autoimmune encephalitis is characterized by formation of antibodies against cell surface proteins. Antibodies against the gamma-aminobuturic acidB (GABAB) receptor lead to limbic encephalitis, drug-resistant seizures, confusion, cognitive impairment and changed behaviour. Some patients present with status epilepticus. GABAB encephalitis is associated with small-cell lung cancer or neuroendocrine lung tumour. This is a case report of a patient having status epilepticus due to GABAB encephalitis. In cases which are presumed to be autoimmune it is important that treatment starts immediately instead of awaiting antibody confirmation...
July 24, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28782512/quantitative-expression-and-localization-of-gabab-receptor-protein-subunits-in-hippocampi-from-patients-with-refractory-temporal-lobe-epilepsy
#7
REVIEW
Mariam A Sheilabi, Dev Battacharyya, Laura Caetano, Maria Thom, Markus Reuber, John S Duncan, Alessandra P Princivalle
This study investigates GABAB protein expression and mRNA levels in three types of specimens. Two types of specimens from patients with temporal lobe epilepsy (TLE), secondary to hippocampal sclerosis, sclerotic hippocampal samples (TLE-HS), and tissue from the structurally preserved non-spiking ipsilateral superior temporal gyrus (TLE-STG) removed from the same patient during epilepsy surgery; and third specimen is hippocampal tissue from individuals with no history of epilepsy (post-mortem controls, PMC)...
August 3, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28768196/a-cooperative-mechanism-involving-ca-2-permeable-ampa-receptors-and-retrograde-activation-of-gabab-receptors-in-interpeduncular-nucleus-plasticity
#8
Peter Koppensteiner, Riccardo Melani, Ipe Ninan
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway, which connects the limbic forebrain to the midbrain, has recently been implicated in aversive behaviors. The MHb-IPN circuit is characterized by a unique topographical organization, an excitatory role of GABA, and a prominent co-release of neurotransmitters and neuropeptides. However, little is known about synaptic plasticity in this pathway. An application of a high-frequency stimulation resulted in a long-lasting potentiation of glutamate release in IPN neurons...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28767433/association-of-myelinated-primary-afferents-impairment-with-mechanical-allodynia-in-diabetic-peripheral-neuropathy-an-experimental-study-in-rats
#9
Chenlong Liao, Min Yang, Wenxiang Zhong, Pengfei Liu, Wenchuan Zhang
To investigate the mechanisms underlying the efficacy of surgical treatment for painful diabetic peripheral neuropathy. Rats were initially divided into 3 groups (I, control rats, II, streptozotocin-induced diabetic rats, III, streptozotocin-induced diabetic rats with latex tube encircling the sciatic nerve without compression). When mechanical allodynia (MA) became stable in the third week, one third of group III rats were sacrificed and the remainder were further divided into subgroups depending on whether the latex tube was removed...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28756462/effects-of-gaba-b-receptor-positive-modulator-on-ketamine-induced-psychosis-relevant-behaviors-and-hippocampal-electrical-activity-in-freely-moving-rats
#10
Jingyi Ma, L Stan Leung
RATIONALE: Decreased GABAB receptor function is proposed to mediate some symptoms of schizophrenia. OBJECTIVES: In this study, we tested the effect of CGP7930, a GABAB receptor positive allosteric modulator, on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in behaving rats. METHODS: Electrodes were bilaterally implanted into the hippocampus, and cannulae were placed into the lateral ventricles of Long-Evans rats...
July 29, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28753481/baclofen-and-naltrexone-effects-on-alcohol-self-administration-comparison-of-treatment-initiated-during-abstinence-or-ongoing-alcohol-access-in-baboons
#11
August F Holtyn, Barbara J Kaminski, Elise M Weerts
BACKGROUND: Baclofen, a GABAB receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access...
July 18, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28742985/gabab-receptors-suppress-burst-firing-in-reticular-thalamic-neurons
#12
Stuart M Cain, Esperanza Garcia, Zeina Waheed, Karen L Jones, Trevor J Bushell, Terrance P Snutch
Burst-firing in thalamic neurons is known to play a key role in mediating thalamocortical (TC) oscillations that are associated with non-REM sleep and some types of epileptic seizure. Within the TC system the primary output of GABAergic neurons in the reticular thalamic nucleus (RTN) is thought to induce the de-inactivation of T-type calcium channels in thalamic relay (TR) neurons, promoting burst-firing drive to the cortex and the propagation of TC network activity. However, RTN neurons also project back onto other neurons within the RTN...
July 25, 2017: Channels
https://www.readbyqxmd.com/read/28734870/elucidation-of-the-neural-circuits-activated-by-a-gabab-receptor-positive-modulator-relevance-to-anxiety
#13
REVIEW
Riccardo Pizzo, Olivia F O'Leary, John F Cryan
Although there is much evidence for a role of GABAB receptors in the pathophysiology of anxiety, the underlying neuronal mechanisms are largely unclear. The GABAB receptor allosteric positive modulator, GS39783, exerts anxiolytic effects without interfering with GABAB-mediated modulation of body temperature, cognitive performance and locomotor activity thus offering advantages over GABAB receptor agonists. However, the precise neural circuits underlying the anxiolytic effects of GS39783 are unknown. The aim of the present study was to identify brain structures and associated neuronal circuits that are modulated by GS39783 under either basal or mild stress conditions...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28726484/annals-express-experience-with-newer-central-nervous-system-autoantibodies
#14
Abid Karim, Saiju Jacob
In the last decade, a large number of neuronal cell-surface antibodies have been described which are responsible for a range of neuroimmunological central nervous system disorders. Unlike the paraneoplastic antibodies which target intracellular antigens, these antibodies appear to be pathogenic and hence identification and prompt treatment can make a substantial impact on clinical outcomes of these patients. We review the common antibodies against the ionotropic Glutamate receptors (NMDAR, AMPAR), metabotropic Glutamate receptors (mGluR1 and mGluR5), voltage gated potassium channel-complex proteins (LGI1, CASPR2), and other antibodies targeted against Glycine receptor, Glutamic acid decarboxylase (GAD), Gamma Amino Butyric Acid B (GABAB), Dopamine-2-receptor (D2R) and Dipeptidyl-peptidase-like protein 6 (DPPX)...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28713569/kctd12-modulation-of-gaba-b-receptor-function
#15
Melody Li, Carol J Milligan, Haiyan Wang, Andrew Walker, Leonid Churilov, Andrew J Lawrence, Christopher A Reid, Seth C Hopkins, Steven Petrou
The molecular composition and functional diversity of native GABAB receptors (GABABR) are still poorly understood, thus hindering development of selective GABABR ligands. Potassium channel tetramerization domain-containing protein (KCTD) 12 is a GABABR auxiliary subunit and mouse KCTD12 can alter GABABR function. In this study, we sought to characterize the effects of human KCTD12 on GABABR kinetics and pharmacology, using an automated electrophysiological assay. Seizure susceptibility and ethanol consumption were also investigated in a KCTD12 knockout mouse model...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28704576/psychosis-an-autoimmune-disease
#16
REVIEW
Adam Aj Al-Diwani, Thomas A Pollak, Sarosh R Irani, Belinda R Lennox
Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28678402/inhibitory-modulation-of-medial-prefrontal-cortical-activation-on-lateral-orbitofrontal-cortex-amygdala-information-flow
#17
Chun-Hui Chang, Ta-Wen Ho
KEY POINTS: The basolateral complex of the amygdala (BLA) receives input from the lateral orbitofrontal cortex (lOFC) for cue-outcome contingencies and the medial prefrontal cortex (mPFC) for emotion control. Here we examined how the mPFC modulates lOFC-BLA information flow. We found that the majority of BLA neurons responsive to lOFC stimulation were also responsive to mPFC stimulation. Activation of the mPFC exerted an inhibitory modulation of the lOFC-BLA pathway, which was reversed with intra-amygdala blockade of GABAergic receptors...
July 5, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28675819/anti-neuronal-autoantibodies-in-both-drug-responsive-and-resistant-focal-seizures-with-unknown-cause
#18
Gokcen Gozubatik-Celik, Cigdem Ozkara, Canan Ulusoy, Aysegul Gunduz, Sakir Delil, Naz Yeni, Erdem Tuzun
BACKGROUND: and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients. METHOD: Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies...
June 17, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28662343/effect-of-chronic-%C3%AE-hydroxybutyrate-ghb-administration-on-ghb-toxicokinetics-and-ghb-induced-respiratory-depression
#19
Bridget L Morse, Gurkishan S Chadha, Melanie A Felmlee, Kristin E Follman, Marilyn E Morris
BACKGROUND: γ-hydroxybutyrate (GHB) has a high potential for illicit use; overdose of this compound results in sedation, respiratory depression and death. Tolerance to the hypnotic/sedative and electroencephalogram effects of GHB occurs with chronic GHB administration; however, tolerance to respiratory depression has not been evaluated. GHB toxicodynamic effects are mediated predominantly by GABAB receptors. Chronic treatment may affect monocarboxylate transporters (MCTs) and alter the absorption, renal clearance and brain uptake of GHB...
June 29, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28662295/%C3%AE-9-containing-nicotinic-acetylcholine-receptors-and-the-modulation-of-pain
#20
REVIEW
Arik J Hone, Denis Servent, J Michael McIntosh
Neuropathic pain is a complex and debilitating syndrome for which there are few effective pharmacological treatments. Opioid-based medications are initially effective for acute pain but tolerance to their analgesic effects quickly develops and long-term use often leads to physical dependence and addiction. Furthermore, neuropathic pain is generally resistant to non-steroidal anti-inflammatory drugs. Other classes of medications including antidepressants, antiepileptics, and voltage-gated calcium channel (VGCC) inhibitors are only partially effective in most patients, may be associated with significant side effects, and have few disease modifying effects on the underlying pathology...
June 29, 2017: British Journal of Pharmacology
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