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 b ulbectomy (OBX) animal model of depression, where GABA(B) receptor bin ding sites have been shown to decrease markedly at specific time point s after OBX. However, as no detailed time course of events has been de termined, the present study investigated the effects of OBX on high-af finity 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 increas es (40-60%) in B(max) values of high affinity GABA(A) receptors were o bserved in the frontal cortex throughout the period investigated follo wing OBX. B(max) values in the hippocampus increased significantly aft er 1 week (53%) but were not statistically significant thereafter. No changes in GABA(A) binding parameters were observed in the hypothalamu s or cerebellum. Conversely, GABA(B) receptor densities were significa ntly decreased in the frontal cortex after 1 (- 38%) and 2 (- 41%) wee ks and moderately decreased 3 and 4 weeks (- 27 and - 23%, respectivel y) after OBX, while in the cerebellum they were significantly increase d 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 re ceptor binding sites or beta-adrenoceptors were not modified throughou t the time course. GABAergic transmission, reflected by changes in GAB A(A) and GABA(B) receptor density in the frontal cortex, may be altere d in OBX rats. The persistence of the change in GABA(A) receptor densi ty, contrasting with the transient change in GABA(B) receptors, sugges ts that the former, rather than the latter, is more likely to be relat ed to the long-lasting behavioral deficits induced by OBX.