Hippocampal partial kindling decreased hippocampal GABAB receptor efficacy and wet dog shakes in rats

To test the hypothesis that GABAB receptor efficacy in the behaving rat decreases after partial hippocampal kindling, we measured GABAB receptor efficacy by the number of wet dog shakes (WDSs) induced by baclofen (5 mM in 0.2 μL of saline) infusion into the dorsal hippocampus; these WDSs were blocked by prior infusion of GABAB receptor antagonist CGP55845A. Rats were given 15 afterdischarges (ADs) evoked in CA1 over 3 days or control stimulations. The partially kindled rats (after 15 ADs) showed a significant decrease in baclofen-induced WDSs as compared to control rats, on days 1, 4 and 21 after kindling. In contrast, kindled and control rats did not show a significant difference in WDSs induced by hippocampal infusion of GABAA receptor antagonist bicuculline. Also, the number of WDSs induced after subcutaneous injection of serotonin-2A/2C agonist ± 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane was not different between kindled and control rats on 4 and 21 days after kindling. We further tested the hypothesis that the decrease in hippocampal AD-induced WDSs during kindling is caused by a decrease in GABAB receptor efficacy. However, we found no convincing evidence to support the latter hypothesis since the AD-induced WDSs were not suppressed by hippocampal infusion of CGP55845A, with the exception that CGP55845A infusion into ventral hippocampus suppressed both hippocampal ADs and WDSs. Together with results derived from previous electrophysiological studies in vitro, it is suggested that a decrease of GABAB receptor, possibly GABAB autoreceptor, efficacy may explain the decrease of baclofen-induced WDSs after hippocampal kindling.