scholarly journals Different Residues in the GABAA Receptor Benzodiazepine Binding Pocket Mediate Benzodiazepine Efficacy and Binding

2011 ◽  
Vol 80 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Elaine V. Morlock ◽  
Cynthia Czajkowski
Keyword(s):  
Gabaa Receptor ◽  
Binding Pocket ◽  
Benzodiazepine Binding

Identification of amino acid residues responsible for the α5  subunit binding selectivity of L-655,708, a benzodiazepine binding site ligand at the GABAA receptor

2001 ◽  
Vol 77 (2) ◽  
pp. 445-451 ◽  
Author(s):  
M. Anna Casula ◽  
Frances A. Bromidge ◽  
Gopalan V. Pillai ◽  
Peter B. Wingrove ◽  
Karine Martin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Gabaa Receptor ◽  
Amino Acid Residues ◽  
Binding Selectivity ◽  
Benzodiazepine Binding

scholarly journals Ligands of the GABAA Receptor Benzodiazepine Binding Site

2006 ◽  
Vol 5 (2) ◽  
pp. 125-144 ◽  
Author(s):  
Qinmi Wang ◽  
Yifan Han ◽  
Hong Xue
Keyword(s):  
Binding Site ◽  
Gabaa Receptor ◽  
Benzodiazepine Binding

Computer-aided design of selective ligands of the benzodiazepine-binding site of the GABAA receptor

2008 ◽  
Vol 422 (1) ◽  
pp. 227-230 ◽  
Author(s):  
V. I. Chupakhin ◽  
S. V. Bobrov ◽  
E. V. Radchenko ◽  
V. A. Palyulin ◽  
N. S. Zefirov
Keyword(s):  
Binding Site ◽  
Gabaa Receptor ◽  
Computer Aided Design ◽  
Selective Ligands ◽  
Computer Aided ◽  
Benzodiazepine Binding ◽  
Aided Design

scholarly journals Cocaine effects on mouse incentive-learning and human addiction are linked to α2 subunit-containing GABAA receptors

2010 ◽  
Vol 107 (5) ◽  
pp. 2289-2294 ◽  
Author(s):  
Claire I. Dixon ◽  
Hannah V. Morris ◽  
Gerome Breen ◽  
Sylvane Desrivieres ◽  
Sarah Jugurnauth ◽  
...  
Keyword(s):  
Behavioral Sensitization ◽  
Binding Pocket ◽  
Receptor Subtype ◽  
Medium Spiny Neurons ◽  
Gabaergic Neurotransmission ◽  
Spiny Neurons ◽  
Benzodiazepine Binding ◽  
Necessary And Sufficient ◽  
The Brain

Because GABAA receptors containing α2 subunits are highly represented in areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and amygdala, regions intimately involved in signaling motivation and reward, we hypothesized that manipulations of this receptor subtype would influence processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of mice with α2 gene deletion showed reduced synaptic GABAA receptor-mediated responses. Behaviorally, the deletion abolished cocaine’s ability to potentiate behaviors conditioned to rewards (conditioned reinforcement), and to support behavioral sensitization. In mice with a point mutation in the benzodiazepine binding pocket of α2-GABAA receptors (α2H101R), GABAergic neurotransmission in medium spiny neurons was identical to that of WT (i.e., the mutation was silent), but importantly, receptor function was now facilitated by the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In α2H101R, but not WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor activity, and when given systemically and repeatedly, induced behavioral sensitization. These data indicate that activation of α2−GABAA receptors (most likely in NAcc) is both necessary and sufficient for behavioral sensitization. Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.

scholarly journals Human locus coeruleus neurons express the GABAA receptor γ2 subunit gene and produce benzodiazepine binding

2010 ◽  
Vol 477 (2) ◽  
pp. 77-81 ◽  
Author(s):  
Kati S. Hellsten ◽  
Saku T. Sinkkonen ◽  
Thomas M. Hyde ◽  
Joel E. Kleinman ◽  
Terttu Särkioja ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Gabaa Receptor ◽  
Subunit Gene ◽  
Benzodiazepine Binding
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