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

Abstract

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.

• Authors: F H Lin, Z Cao, D A Hosford
• Journal: Brain research (Brain Res) Vol. 608 Issue 1 Pg. 101-6 (Apr 09 1993) ISSN: 0006-8993 [Print] Netherlands
• PMID: 8388308 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Receptors, GABA-A
• Receptors, N-Methyl-D-Aspartate
• Baclofen

Topics

• Animals
• Baclofen (metabolism)
• Biomarkers (chemistry)
• Disease Models, Animal
• Epilepsy, Absence (metabolism)
• Male
• Mice
• Mice, Neurologic Mutants
• Radioligand Assay
• Receptors, GABA-A (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Reproducibility of Results