title: To what extent is it possible to dissociate the anxiolytic and sedative/hypnotic properties of GABAA receptors modulators?
abstract: The relatively common view indicates a possible dissociation between the anxiolytic and sedative/hypnotic properties of benzodiazepines (BZs). Indeed, GABAA receptor (GABAAR) subtypes have specific cerebral distribution in distinct neural circuits. Thus, GABAAR subtype-selective drugs may be expected to perform distinct functions. However, standard behavioral test assays provide limited direction towards highlighting new action mechanisms of ligands targeting GABAARs. Automated behavioral tests, lack sensitivity as some behavioral characteristics or subtle behavioral changes of drug effects or that are not considered in the overall analysis (Ohl et al., 2001) and observation-based analyses are not always performed. In addition, despite the use of genetically engineered mice, any possible dissociation between the anxiolytic and sedative properties of BZs remains controversial. Moreover, the involvement the different subtypes of GABAAR subtypes in the anxious behavior and the mechanism of action of anxiolytic agents remains unclear since there has been little success in the pharmacological investigations so far. This raises the question of the involvement of the different subunits in anxiolytic-like and/or sedative effects; and the actual implication of these subunits, particularly, α-subunits in the modulation of sedation and/or anxiety-related disorders. This present review was prompted by several conflicting studies on the degree of involvement of these subunits in anxiolytic-like and/or sedative effects. To this end, we explored the GABAergic system, particularly, the role of different subunits containing synaptic GABAARs. We report herein the targeting gene encoding the different subunits and their contribution in anxiolytic-like and/or sedative actions, as well as, the mechanism underlying tolerance to BZs.
authors: Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedecine, Normandy University, France; Department of Medical Biochemistry, Rouen University Hospital, Rouen, France. Electronic address: abdeslam.chagraoui@univ-rouen.fr.
authors: A
authors: A
authors: Chagraoui
authors: Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedecine, Normandy University, France.
authors: M
authors: M
authors: Skiba
authors: Department of Pharmacology, Rouen University Hospital, Rouen, and INSERM U1096, Laboratory of New Pharmacological Targets for Endothelial Protection and Heart Failure, Institute for Research and Innovation in Biomedicine, Normandy University, France.
authors: C
authors: C
authors: Thuillez
authors: Department of Psychiatry, University Hospital Cochin (site Tarnier), University of Paris-Descartes and INSERM U 894 Laboratory of Psychiatry and Neurosciences, Paris, France.
authors: F
authors: F
authors: Thibaut
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D018757:GABA Modulators / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A
keywords: Anxiolytic; Benzodiazepine; GABA(A) receptors; Sedation; Subunits; Tolerance