Hippocampal partial kindling decreased hippocampal GABAB receptor efficacy and wet dog shakes in rats.
To test the hypothesis that GABA(B) receptor efficacy in the behaving rat decreases after partial hippocampal kindling, we measured GABA(B) receptor efficacy by the number of wet dog shakes (WDSs) induced by baclofen (5mM in 0.2muL of saline) infusion into the dorsal hippocampus; these WDSs were blocked by prior infusion of GABA(B) 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 GABA(A) 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 GABA(B) 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 GABA(B) receptor, possibly GABA(B) autoreceptor, efficacy may explain the decrease of baclofen-induced WDSs after hippocampal kindling.
Leung
L Stan
LS
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A5C1. sleung@uwo.ca
Shen
Bixia
B
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D018755:GABA Agonists; D018756:GABA Antagonists / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018080:Receptors, GABA-B / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
D000662:Amphetamines; D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; D017366:Serotonin Receptor Agonists; C085075:CGP 55845A; D001418:Baclofen; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine