In:
European Journal of Neuroscience, Wiley, Vol. 24, No. 1 ( 2006-07), p. 167-174
Abstract:
The majority of inhibitory neurotransmission in the brain is mediated by the γ‐aminobutyric acid (GABA) type A (GABA A ) receptor. The anticonvulsant loreclezole largely acts by potentiating GABA A receptors containing β2 and β3 subunits. We used a genetically modified mouse containing a loreclezole‐insensitive β2 subunit (β2N265S) to determine the role of this subunit in mediating the sedative and anticonvulsive effects of loreclezole. Sedation was assessed by measuring spontaneous locomotor activity and beam walking performance, and anticonvulsant efficacy was determined by pentylenetetrazole (PTZ) and amygdala kindling‐induced seizures. The β2N265S mice did not exhibit loreclezole‐mediated sedation as shown by normal locomotor activity and beam walking performance. However, loreclezole also failed to provide significant protection against PTZ‐induced seizures in the β2N265S mice. Reduced efficacy against amygdala‐kindled seizures, both acutely and over a 13‐day chronic dosing study, was also observed in β2N265S mice. These results suggest that the majority of the sedative effects and a significant proportion of the anticonvulsant efficacy of loreclezole are mediated via β2‐containing GABA A receptors.
Type of Medium:
Online Resource
ISSN:
0953-816X
,
1460-9568
DOI:
10.1111/ejn.2006.24.issue-1
DOI:
10.1111/j.1460-9568.2006.04890.x
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
2005178-5
SSG:
12