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Caitlin A Wotton, Elizabeth F Quon, Ashley C Palmer, Lane K Bekar
Both serotonin (5HT) and stress exert changes in cortical inhibitory tone to shape activity of cortical networks. As astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways in rapid corticosterone (CORT) and 5HT effects on cortical inhibition. We used a paired-pulse paradigm (P1 & P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5HT decreases amplitude of the first pulse P1, while increasing the amplitude of P2 (increase frequency transmission)...
March 15, 2018: Journal of Neuroendocrinology
Juan Francisco Rodríguez-Landa, Jonathan Cueto-Escobedo, Luis Ángel Flores-Aguilar, Gilberto Uriel Rosas-Sánchez, María de Jesús Rovirosa-Hernández, Francisco García-Orduña, Miguel Carro-Juárez
BACKGROUND: Montanoa frutescens and Montanoa grandiflora have been indistinctly used for centuries in traditional Mexican medicine for reproductive impairments, anxiety, and mood disorders. Preclinical studies support their aphrodisiac and anxiolytic properties, but their effects on mood are still unexplored. METHODS: The effects of 25 and 50 mg/kg of M frutescens and M grandiflora extracts were evaluated on days 1, 7, 14, 21, and 28 of treatment, and compared with fluoxetine (1 mg/kg) and Remotiv (7...
January 2018: J Evid Based Integr Med
Li-Yuan Chen, Maxime Lévesque, Mauro Cataldi, Massimo Avoli
The muscarinic receptor agonist carbachol (CCh) can induce activity in the theta range (4 - 15 Hz) in the entorhinal cortex (EC), but the underlying network mechanisms remain unclear. Here, we investigated the interplay between interneurons and principal cells in the EC during CCh-induced theta-like field oscillations in an in vitro brain slice preparation using tetrodes. Field oscillations at 10.1 Hz (IQR = 9.5 - 10.9 Hz) occurred during bath application of CCh (100 μM; n = 32 experiments) and were associated with single-unit (n = 189) firing...
March 10, 2018: Neuroscience
Amanda M Barkley-Levenson, Frances A Lagarda, Abraham A Palmer
BACKGROUND: Glyoxalase 1 (GLO1) is an enzyme that metabolizes methylglyoxal (MG), which is a competitive partial agonist at GABAA receptors. Inhibition of GLO1 increases concentrations of MG in the brain and decreases binge-like ethanol drinking. The present study assessed whether inhibition of GLO1, or genetic over expression of Glo1, would also alter the locomotor effects of ethanol, which might explain reduced ethanol consumption following GLO1 inhibition. We used the prototypical GABAA receptor agonist muscimol as a positive control...
March 12, 2018: Alcoholism, Clinical and Experimental Research
Pengmin Qin, Niall W Duncan, David Yen-Ting Chen, Chi-Jen Chen, Li-Kai Huang, Zirui Huang, Chien-Yuan E Lin, Christine Wiebking, Che-Ming Yang, Georg Northoff, Timothy Lane
Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioural states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18 F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and [18 F]-flumazenil PET in a separate group (n = 19)...
March 9, 2018: Neuroscience
Alexander J Riordan, Ari W Schaler, Jenny Fried, Tracie A Paine, Janice E Thornton
The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP...
February 27, 2018: Psychoneuroendocrinology
Travis T Mallard, James R Ashenhurst, K Paige Harden, Kim Fromme
GABRA2, the gene encoding the α2 subunit of the GABAA receptor, potentially plays a role in the etiology of problematic drinking, as GABRA2 genotype has been associated with subjective response to alcohol and other alcohol-related reward processes. The GABRA2 gene has also been associated with illicit drug use, but the extent to which associations with drug use are independent of associations with alcohol use remains unclear, partly because most previous research has used a cross-sectional design that cannot discriminate comorbidity at the between-person level and co-occurrence within-persons...
February 2018: Journal of Abnormal Psychology
Dilara Nemutlu Samur, Rana Arslan, Sule Aydın, Nurcan Bektas
The purpose of this study is to assess the possible anti-allodynic and antihyperalgesic effect of valnoctamide, an amide derivative of valproic acid, at the doses of 40, 70 and 100mg/kg (i.p.) in neuropathic pain model induced by chronic constriction injury in rats, by using dynamic plantar test and plantar test (Hargreaves method), and to evaluate that the possible role of certain serotonin, noradrenergic, opioid and GABAergic receptors by pre-treatment with 1mg/kg (i.p.) ketanserin, yohimbine, naloxone and 0...
March 6, 2018: European Journal of Pharmacology
Keite Lira de Almeida França, Antônio-Carlos Guimarães de Almeida, Stephen E Saddow, Luiz Eduardo Canton Santos, Carla Alessandra Scorza, Fulvio Alexandre Scorza, Antônio Márcio Rodrigues
The role of GABAergic neurotransmission on epileptogenesis has been the subject of speculation according to different approaches. However, it is a very complex task to specifically consider the action of the GABAa neurotransmitter, which, in its dependence on the intracellular level of Cl- , can change its effect from inhibitory to excitatory. We have developed a computational model that represents the dentate gyrus and is composed of three different populations of neurons (granule cells, interneurons and mossy cells) that are mutually interconnected...
March 8, 2018: Scientific Reports
John Peyton Bohnsack, Benjamin A Hughes, Todd K O'Buckley, Kamyra Edokpolor, Joyce Besheer, A Leslie Morrow
Alcohol use disorders are chronic debilitating diseases characterized by severe withdrawal symptoms that contribute to morbidity and relapse. GABAA receptor (GABAA R) adaptations have long been implicated in the chronic effects of alcohol and contribute to many withdrawal symptoms associated with alcohol dependence. In rodents, GABAA R hypofunction results from decreases in Gabra1 expression, although the underlying mechanism controlling Gabra1 expression after chronic ethanol exposure is still unknown. We found that chronic ethanol exposure using either ethanol gavage or two-bottle choice voluntary access paradigms decreased Gabra1 expression and increased Hdac2 and Hdac3 expression...
February 27, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Lih-Chu Chiou, Hsin-Jung Lee, Margot Ernst, Wei-Jan Huang, Jui-Feng Chou, Hon-Lie Chen, Akihiro Mouri, Liang-Chieh Chen, Marco Treven, Takayoshi Mamiya, Pi-Chuan Fan, Daniel E Knutson, Chris Witzigmann, James Cook, Werner Sieghart, Toshitaka Nabeshima
BACKGROUND AND PURPOSE: The pathophysiological role of α6 subunit-containing GABAA receptors (α6GABAA Rs), which are mainly expressed in cerebellar granule cells, remains unclear. Recently, we demonstrated that hispidulin, a flavonoid isolated from a local herb that remitted a patient's intractable motor tics, attenuated methamphetamine-induced hyperlocomotion in mice as a positive allosteric modulator (PAM) of cerebellar α6GABAA Rs. Here, using hispidulin and a selective α6GABAA R PAM, the pyrazoloquinolinone Compound 6, we revealed an unprecedented role of cerebellar α6GABAA Rs in disrupted prepulse inhibition (PPI), which reflects sensorimotor gating deficits manifested in several neuropsychiatric disorders...
March 8, 2018: British Journal of Pharmacology
Panos Zanos, Scott M Thompson, Ronald S Duman, Carlos A Zarate, Todd D Gould
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites...
March 7, 2018: CNS Drugs
Md Shafiullah Shajib, Ridwan B Rashid, Long C Ming, Shanta Islam, Md Moklesur R Sarker, Lutfun Nahar, Satyajit D Sarker, Bidyut K Datta, Mohammad A Rashid
Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia , an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone ( 1 ), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) ( 2 ), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone ( 3 ), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone ( 4 ), isolated and identified from N...
2018: Frontiers in Pharmacology
Kellie A Woll, Xiaojuan Zhou, Natarajan V Bhanu, Benjamin A Garcia, Manuel Covarrubias, Keith W Miller, Roderic G Eckenhoff
Most general anesthetics enhance GABA type A (GABAA ) receptor activity at clinically relevant concentrations. Sites of action of volatile anesthetics on the GABAA receptor remain unknown, whereas sites of action of many intravenous anesthetics have been identified in GABAA receptors by using photolabeling. Here, we used photoactivatable analogs of isoflurane (AziISO) and sevoflurane (AziSEVO) to locate their sites on α1 β3 γ2L and α1 β3 GABAA receptors. As with isoflurane and sevoflurane, AziISO and AziSEVO enhanced the currents elicited by GABA...
March 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sean M Bugel, Robert L Tanguay
The comparative analysis of complex behavioral phenotypes is valuable as a reductionist tool for both drug discovery and defining chemical bioactivity. Flavonoids are a diverse class of chemicals that elicit robust neuroactive and hormonal actions, though bioactivity information is limited for many, particularly for neurobehavioral endpoints. Here, we used a zebrafish larval chemomotor response (LCR) bioassay to comparatively evaluate a suite of 24 flavonoids, and in addition a panel of 30 model neuroactive compounds representing diverse modes of action (e...
February 27, 2018: Toxicology and Applied Pharmacology
Priyanka Dutta, Leila Dargahi, Kara E O'Connell, Ashini Bolia, Banu Ozkan, Andreas W Sailer, Kumlesh K Dev
Parkin associated endothelin like receptor (PAELR) is G-protein coupled and ubiquitinated by parkin, promoting its degradation. In autosomal recessive Parkinson's disease, mutations in parkin lead to PAELR aggregation in the endoplasmic reticulum (ER), ER stress, neurotoxicity and cell death. We have identified previously that the protein kinase C interacting protein (PICK1) interacts with and regulates the expression and cell toxicity of PAELR. Here, we experimentally identify and provide in-silico modelling of a novel interaction between PAELR and GABARAPL2 (γ-aminobutyrate type A receptor associated protein like 2), which is an autophagosome-specific Ub-like protein implicated in vesicle trafficking and autophagy...
February 26, 2018: Neuroscience Letters
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
Hank Bink, Madineh Sedigh-Sarvestani, Ivan Fernandez-Lamo, Lohith Kini, Hoameng Ung, Duygu Kuzum, Flavia Vitale, Brian Litt, Diego Contreras
New devices that use targeted electrical stimulation to treat refractory localization-related epilepsy have shown great promise, though it is not well known which targets most effectively prevent the initiation and spread of seizures. To better understand how the brain transitions from healthy to seizing on a local scale, we induced focal epileptiform activity in the visual cortex of five anesthetized cats with local application of the GABAA blocker picrotoxin while simultaneously recording local field potentials on a high-resolution electrocorticography array and laminar depth probes...
February 28, 2018: Journal of Neurophysiology
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
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