Differential effects of olfactory bulbectomy on GABAA and GABAB receptors in the rat brain.
GABAergic mechanisms have been implicated in the bilateral olfactory bulbectomy (OBX) animal model of depression, where GABAB receptor binding sites have been shown to decrease markedly at specific time points after OBX. However, as no detailed time course of events has been determined, the present study investigated the effects of OBX on high-affinity GABAA, GABAB, beta-adrenergic, and benzodiazepine receptor binding parameters in membrane preparations from rat brain regions at weekly intervals (1-4 weeks) after OBX. Persistent significant increases (40-60%) in Bmax values of high affinity GABAA receptors were observed in the frontal cortex throughout the period investigated following OBX. Bmax values in the hippocampus increased significantly after 1 week (53%) but were not statistically significant thereafter. No changes in GABAA binding parameters were observed in the hypothalamus or cerebellum. Conversely, GABAB receptor densities were significantly decreased in the frontal cortex after 1 (-38%) and 2 (-41%) weeks and moderately decreased 3 and 4 weeks (-27 and -23%, respectively) after OBX, while in the cerebellum they were significantly increased after 1 week (96%) and returned to sham-operated levels by 3 weeks. No changes in GABAB receptor binding parameters were observed in the hippocampus or hypothalamus. Binding parameters for benzodiazepine receptor binding sites or beta-adrenoceptors were not modified throughout the time course. GABAergic transmission, reflected by changes in GABAA and GABAB receptor density in the frontal cortex, may be altered in OBX rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Dennis
T
T
Department of Psychiatry, McGill University, Montréal, Québec, Canada.
Beauchemin
V
V
Lavoie
N
N
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009830:Olfactory Bulb / Q000502:physiology*; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C033394:CGP 12177