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Developmental neurobiology of nociception
Published in Pamela E Macintyre, Suellen M Walker, David J Rowbotham, Clinical Pain Management, 2008
Inhibitory mechanisms may not be fully mature in early life (see Table 2.1). Fast inhibitory transmission is mediated by gamma-aminobutyric acid (GABA) and glycine receptors, both of which undergo developmental changes in subunit expression that influence channel kinetics.2 In the hippocampus, GABA initially produces depolarizing rather than hyperpolarizing currents, as the intracellular chloride concentration remains high until the potassium-chloride cotransporter KCC2 is upregulated later in development.51, 59 However, GABAergic inhibition may mature earlier in the spinal cord. In dorsal horn slices, although GABA produced depolarization in a proportion of cells at P0–2 this was insufficient to produce action potentials, and by P6-7 only the adult pattern of hyperpolarizing responses was recorded.49 Application of the GABAA-antagonist gabazine to the spinal cord in vivo produced a similar degree of increased firing at P3 and P21, suggesting that intrinsic spinal GABAergic inhibition is functional during early life.50 Although GABA does not appear to have significant direct excitatory effects in the spinal cord, the overall response to GABA activation is also influenced by descending inputs.60 Although local inhibition within the spinal cord can be demonstrated in early life, modulation by descending inputs may initially result in an overall facilitatory effect.
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
were chronically exposed to 3a5p, suggesting that uncoupling is an active process that requires intact cells. Co-treatment of cultures with 3a5p and gabazine did not prevent the loss of 3a5p potentiation of 3H-flunitrazepam binding, but did block the decrease in GABA potentiation of 3H-flunitrazepam binding,14 demonstrating that 3a5p-induced steroid-benzodiazepine site uncoupling and GABA-benzodiazepine site uncoupling are distinct. This result suggests that the GABA-benzodiazepine site uncoupling is likely an indirect consequence of potentiation of GABA transmission by 3a5p, whereas steroid-GABA site uncoupling is triggered by a different mechanism. Although resistant to gabazine, steroid-benzodiazepine site uncoupling was significantly decreased by co-treatment with the noncompetitive GABAA receptor
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
The data mentioned above suggest that the propofol action can be mediated by GABAA receptors in the SCN. In vitro, GABA can induce phase-shifts in clock cells kept in culture and the daily treatment by GABA synchronizes cultured clock cells (Liu and Reppert 2000). In SCN explants of luciferase transgenic rats, the suppression of Per2 expression observed after sevoflurane application is blocked by the co-application of both GABAA and GABAB receptor antagonists, suggesting an GABergic mechanism (Matsuo et al. 2016). In vivo, the GABAA receptor activation by muscimol (a selective GABAA receptors agonist) during the mid-subjective day not only induces phase advances of locomotor activity in hamsters (Smith et al. 1989), but also suppresses Per1 mRNA and Per2 mRNA expression in the SCN of both diurnal and nocturnal rodents (Ehlen et al. 2006; Novak et al. 2006). Yokota and al., report also phase advances in hamster locomotor activity and reduced expression of Per1 and Per2 in the SCN 1 and 2 h after injection of brotizolam (which is a GABAA receptor agonist belongs to benzodiazepines family) during mid-subjective daytime in hamsters (Yokota et al. 2000). The effects are quite comparable to those observed after propofol injection. However, the injection of muscimol (Smith et al. 1989) or brotizolam (Yokota et al. 2000) during the mid-subjective night leads to phase-delays of locomotor activity, while propofol anaesthesia has no longer any shifting effects at this time of day (Challet et al. 2007). In mutant mice with loss of function of voltage-gated Na+ channel NaV1.1 (which is the primary voltage gate Na+ channel in several classes of GABA interneurons), Han et al. demonstrated important disruption in the circadian master clock with longer circadian period, delayed activity onset and decreased circadian amplitude. This impairment is related to reduction of GABAergic transmission (Han et al. 2012). In a recent abstract, the suppression of Per1 expression in the mPFC of rats following a propofol infusion is described. However, this result is not observed when propofol is co-administered with GABAzine (a GABAA receptor antagonist) (Wang et al. 2016).