35S]TBPS binding sites are decreased in the colliculi of mice with a genetic predisposition to bicuculline-induced seizures

Abstract

Several differences have been found in GABAergic function between the long sleep (LS) and short sleep (SS) mice which were genetically selected for different ethanol-induced sleeptimes, and it has been suggested that these differences may explain their differential ethanol sensitivity. However, these lines also differ in seizure susceptibility, a behavior which may also be mediated by GABAergic pathways. Thus, it is difficult to associate differences in GABA neurochemistry with either of these behaviors, particularly when only two selected lines are used. We measured differences in the density and affinity of the [ 35S]TBPS binding site on the GABA A receptor/Cl − ionophore complex in discrete brain areas; and in order to determine the relationship between receptor binding and behavioral differences, we included mice from 5 of the LS and SS recombinant inbred strains (LS × SS RI) in addition to mice from the LS and SS lines. [ 35S]TBPS binding in sagittal brain sections was analyzed by quantitative autoradiography, and the amount of binding differed depending on whether bicuculline was added to inhibit endogenous GABA binding. In the presence of bicuculline, the number of [ 35S]TBPS sites in SS mice was highest in the colliculi (4.5 ± 0.5 pmol/mg protein), cerebellum (4.8 ± 0.6 pmol/mg), hippocampus (3.2 ± 0.7 pmol/mg) and cortex (2.9 ± 0.3 pmol/mg). The B max was two-fold lower in both superior and inferior colliculi (IC) of LS mice. There were no differences between lines in B max in any other area and in K d values in any area (58 ± 4.0 nM). When we compared [ 35S]TBPS binding in the LS × SS RI strains, B max values in IC were negatively correlated with latency to bicuculline-induced seizures but were not correlated with the duration of ethanol-induced sleeptime. These data support the hypothesis that differences in GABAergic neurochemistry in these mouse lines may not always be related to differences in ethanol sensitivity and point to GABAergic receptors in IC as possibly being involved in determining seizure sensitivity to bicuculline.