Different actions of gabapentin and baclofen in hippocampus from weaver mice.
Hippocampus. 2003-01-01; 13(4): 525-528
DOI: 10.1002/hipo.10131
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1. Hippocampus. 2003;13(4):525-8.
Different actions of gabapentin and baclofen in hippocampus from weaver mice.
Bertrand S(1), Morin F, Lacaille JC.
Author information:
(1)Centre de Recherche en Sciences Neurologiques, Département de Physiologie,
Université de Montréal, Montréal, Quebec, Canada.
The pre- and postsynaptic effects of baclofen, a broad-spectrum
gamma-aminobutyric acid (GABA)B receptor agonist, and gabapentin, a selective
agonist at GABA(B) receptors composed of GABA(B)(1a,2) heterodimers, were
examined in CA1 pyramidal cells using whole-cell patch-clamp recordings in
hippocampal slices from different strains of mice. In slices from C57BL/6 mice,
by means of GABA(B) receptors, gabapentin and baclofen activated outward K+
currents at resting membrane potential. In weaver mice with a Kir3.2 channel
mutation, baclofen and gabapentin failed to activate postsynaptic K+ currents.
However, in littermate controls of weaver mice, gabapentin failed to evoke K+
currents, whereas baclofen activated currents in the same cells. Thus,
postsynaptic actions of gabapentin and baclofen on K+ currents are different in
this mouse strain. Via presynaptic GABA(B) receptors, baclofen significantly
reduced GABA(A) inhibitory postsynaptic currents (IPSCs) in slices from C57BL/6
mice, as well as weaver and control mice. In contrast, gabapentin did not affect
IPSCs significantly in any group of mice. These results indicate that although
baclofen and gabapentin are agonists at postsynaptic GABA(B) receptors positively
coupled to K+ channels, their mechanism of action differs in certain strains of
mice, including the weaver wild-type mice, suggesting a dissociation in their
signaling mechanism and coupling to K+ channels.
DOI: 10.1002/hipo.10131
PMID: 12836919 [Indexed for MEDLINE]