Increased number of GABAB receptors in the lethargic (lh/lh) mouse model of absence epilepsy.


Journal Article

This study begins to explore possible mechanisms underlying the role of GABAB receptors in absence seizures in lethargic (lh/lh) mice. To test the hypothesis that alterations intrinsic to the GABAB receptor underlie enhanced synaptic activation of these receptors in absence seizures, we measured GABA-displaceable [3H]baclofen binding to neocortical plasma membranes prepared from lh/lh and wild (+/+) age-matched congenic mice. The number (Bmax) of binding sites was significantly greater (20%) in lh/lh (4.2 pmol/mg protein, n = 43 pairs, P < 0.02) than in +/+ mice (3.3 pmol/mg protein) in an age-independent manner. Interestingly, the subset of lh/lh mice with greater seizure frequency (40-70 seizures/15 min, measured by bipolar electrodes implanted into neocortex; n = 11) had a significantly greater Bmax (P < 0.003) than the subset with lower seizure frequency (1-10 seizures/15 min; n = 11). The equilibrium dissociation constant (Kd) was unchanged (60 nM in both). The Kd of both strains was inhibited to an equal degree by the nonhydrolysable GTP analogue 5'-guanylimido-diphosphate [Gpp(NH)p]. The increased number of GABAB binding sites was selective, because binding to NMDA sites ([3H]glutamate binding) and to GABAA sites ([3H]muscimol binding) was not significantly different in the two strains. These data suggest that the increased number of GABAB receptors in lh/lh mice underlies enhanced synaptic activation of these receptors. Together with evidence that GABAB receptor activation can produce disinhibition, our data support a role for GABAB receptors in the expression of absence seizures in lh/lh mice.

Full Text

Cited Authors

  • Lin, FH; Cao, Z; Hosford, DA

Published Date

  • April 1993

Published In

Volume / Issue

  • 608 / 1

Start / End Page

  • 101 - 106

PubMed ID

  • 8388308

Pubmed Central ID

  • 8388308

Electronic International Standard Serial Number (EISSN)

  • 1872-6240

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/0006-8993(93)90779-m


  • eng