DIFFERENTIAL-EFFECTS OF OLFACTORY BULBECTOMY ON GABA-A AND GABA-B RECEPTORS IN THE RAT-BRAIN

GABAergic mechanisms have been implicated in the bilateral olfactory bulbectomy (OBX) animal model of depression, where GABA(B) 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 GABA(A), GABA(B), 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 B(max) values of high affinity GABA(A) receptors were observed in the frontal cortex throughout the period investigated following OBX. B(max) values in the hippocampus increased significantly after 1 week (53%) but were not statistically significant thereafter. No changes in GABA(A) binding parameters were observed in the hypothalamus or cerebellum. Conversely, GABA(B) 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 GABA(B) 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 GABA(A) and GABA(B) receptor density in the frontal cortex, may be altered in OBX rats. The persistence of the change in GABA(A) receptor density, contrasting with the transient change in GABA(B) receptors, suggests that the former, rather than the latter, is more likely to be related to the long-lasting behavioral deficits induced by OBX.