LACK OF EFFECT OF BILATERAL LOCUS-COERULEUS LESION AND ANTIDEPRESSANT TREATMENT ON GAMMA-AMINOBUTYRIC ACID(B) RECEPTORS IN THE RAT FRONTAL-CORTEX

The aim of the present study was to investigate whether a disturbance of the central noradrenergic (NA) system could cause changes in gamma-aminobutyric acid(B) (GABA(B)) receptors in the rat frontal cortex. Manipulation of the NA projection to the frontal cortex was achieved by bilateral lesion of the locus coeruleus with 6-hydroxydopamine (6-OHDA) or chronic treatment with the NA reuptake blocker and antidepressant drug, desipramine. Precautions were taken to ensure that the GABA(B) receptor assay was performed optimally and was not confounded by the presence of endogenously generated GABA. The results show conclusively that manipulation of the NA projection did not result in any significant change in the number (Bmax) or affinity (Kd) of GABA(B) receptors in the frontal cortex. These results do not support the hypothesis that hypoactivity of the central NA system can lead to changes in cortical GABA(B) receptors and that antidepressant drugs act by increasing GABA(B) receptor binding in the frontal cortex.