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Role of central GABA in the regulation of blood pressure and the development of hypertension in the SHR
Published in H. Saito, Y. Yamori, M. Minami, S.H. Parvez, New Advances in SHR Research –, 2020
Maarten Van Den Buuse, Geoffrey A. Head
Early studies mainly used intracerebroventricular (i.c.v.) injection of GABA or GABA analogues, but it is clear that this mode of administration does not indicate the precise site of action of these drugs in the brain. It was shown that i.c.v. injection of GABA in anesthetized dogs produced a decrease in blood pressure (Bhargava et al., 1964). Infusion of high doses of GABA into the third ventricle of anesthetized cats similarly caused a decrease of resting blood pressure and furthermore inhibited pressor responses induced by electrical stimulation of the posterior hypothalamus (Philippu et al., 1973). In anesthetized cats, the ix.v. injection of the GABA-A receptor agonist muscimol induced a decrease in blood pressure, heart rate and renal sympathetic nerve activity (Antonaccio et al., 1978b), an effect which could be inhibited by pretreatment with the GABA antagonists bicuculline or picrotoxin. Lev. injection of muscimol also caused inhibition of the pressor responses caused by electrical stimulation in the diencephalon (Antonaccio et al., 1978a).
The Epileptic Gerbil. Neuronal Networks and Actions of Antiepileptic Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
As discussed above, there is strong evidence from neurochemical studies that GABAergic neurotransmission may be impaired in gerbil brain, especially in SN. This may explain the high anticonvulsant potency of GABAmimetic drugs in this species. Löscher et al.31 reported that GABAmimetics, such as the GABA pro-drug cetyl GABA, the GABA degradation inhibitors aminooxyacetic acid (AOAA), and gamma-acetylenic GABA (GAG), the GABA receptor agonist THIP, and the GABA uptake blocker (-)-nipecotic acid ethyl ester, were strikingly more potent to suppress seizures in gerbils than in other genetic animal models of epilepsy and in traditional electrical or chemical mouse or rat models of epilepsy, such as maximal electroshock seizures (MES) or seizures induced by pentylenetetrazol (PTZ). Subsequent studies showed that the same was true for other GABA uptake blockers, such as the novel N-4,4-diphenyl-3-butenyl derivatives of nipecotic acid and guvacine, SKF 89976-A and SKF 100330-A,30 the GABA receptor agonist muscimol,32 and the GABA aminotransferase (GABA-T) inhibitors ethanolamine-O-sulfate (EOS)32 and gamma-vinyl GABA (GVG).33 Interestingly, the effective doses of GVG in gerbils are in the range known to be effective in patients with epilepsy.34 With respect to seizure types in gerbils, the GABA receptor agonists THIP and progabide were almost equally effective to protect against minor and major seizures.35
Uptake and Release of Glutamate and Glutamine in Neurons and Astrocytes in Primary Cultures
Published in Elling Kvamme, Glutamine and Glutamate in Mammals, 1988
Arne Schousboe, Jørgen Drejer, Leif Hertz
The potassium-stimulated glutamate release from cerebellar granule cells has recently been reported to be regulated by the inhibitory amino acid neurotransmitter GABA.13,4344 Under conditions where the neurons have both high- and low-affinity GABA receptors,13,43-45 GABA has been found to inhibit evoked glutamate release.13 This effect of GABA could be mimicked by its agonists muscimol and THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and blocked by its antagonist bicuculline.13 This together with the finding that the GABAb-receptor agonist baclofen46 had no effect13 suggest that the inhibitory effect of GABA on these neurons is mediated by a GABAa receptor.
The neurochemistry of hypnotic suggestion
Published in American Journal of Clinical Hypnosis, 2021
David J. Acunzo, David A. Oakley, Devin B. Terhune
Multiple reports imply that elevated GABA produces increased suggestibility. However, these data come from studies that lacked placebo-controlled trials and robust measures of suggestibility and thus should be considered preliminary. Early research suggested that amobarbital, a GABAA receptor agonist, increases suggestibility (Eysenck & Rees, 1945). Recent research has highlighted how the abuse of benzodiazepines, which include a large number of sedative GABAA agonists, produces automatism amnesia where individuals will perform seemingly automatic behaviors and display elevated suggestibility often followed by anterograde amnesia (Goullé & Anger, 2004; Marc et al., 2000). Benzodiazepines have also been cited as increasing suggestibility in the context of narcotherapy in functional neurological disorder (Rosebush & Mazurek, 2011). Gamma hydroxybutyric acid, a GABAB agonist used in the treatment of narcolepsy and as an anesthetic agent, has similarly been reported to increase suggestibility (e.g., Bismuth, Dally, & Borron, 1997). These encouraging, albeit preliminary, results point to a clear need to more rigorously assess the impact of GABA agonism on suggestibility, including an assessment of mediating factors to distinguish between competing interpretations of these results.
Mechanisms and mode of action of spinal cord stimulation in chronic neuropathic pain
Published in Postgraduate Medicine, 2020
Lonne Heijmans, Elbert A. Joosten
Preclinical studies have established the involvement of the neurotransmitter GABA and the inhibitory GABAergic interneurons in the mechanism underlying tonic SCS mediated analgesia. Extracellular GABA concentrations in the dorsal horn of neuropathic rats were shown to be increased during SCS [4]. Furthermore, Janssen et al. showed reduced intracellular GABA immunoreactivity in the dorsal horn of rats with Partial Sciatic Nerve Ligation (PSNL) after 30 minutes of tonic SCS [5]. From this, it is concluded that tonic SCS induced GABA release into the extracellular space in the spinal dorsal horn and that this is a pivotal mechanism underlying the pain-relieving mechanism of tonic SCS. Intrathecal pharmacological studies have further elucidated and detailed the involvement of this GABAergic mechanism in tonic SCS, demonstrating in particular the GABAB receptor to be very important [6,7]. Importantly these preclinical findings have been translated into the clinic, demonstrating that the synergistic effect of administering a subclinical dose of the GABAB receptor agonist baclofen and tonic SCS turned SCS non-responders into responders [8].
Short-term propofol anaesthesia down-regulates clock genes expression in the master clock
Published in Chronobiology International, 2018
Nawfel Ben-Hamouda, Vincent-Joseph Poirel, Garance Dispersyn, Paul Pévet, Etienne Challet, Laure Pain
Another hypothesis for propofol action is a modulation of the gap junctions in the SCN. These junctions made of connexins are responsible for the intercellular coupling between SCN cells (Aton and Herzog 2005). An ultrastructural study reported the immunocytochemical evidence that these neuronal gap junctions are composed of connexin36 (Rash et al. 2007). Previously, Mantz and colleagues showed that propofol and other general anaesthetics differentially reduce permeability of gap junctions, at least in cultured astrocytes (Mantz et al. 1993). In rat SCN neurons cultured in vitro, the gap junction communication is involved in interneuronal communication and the coupling state between neurons via GABAA receptor. The GABAA receptor agonist muscimol acts as a gap junction blocker (Shinohara et al. 2000). In the same way, connexin36-knockout mice show dampened circadian activity rhythms and a delayed onset of activity during transition to constant darkness, as compared to wild-type mice (Long et al. 2005). Of note, these knockout mice show a greater sensitivity to anaesthetics, including propofol (Jacobson et al. 2011). Together, these data suggest that the phase-shifts induced by propofol anaesthesia may be related to an uncoupling effect between SCN neurons mediated by GABAA receptors.