Flattening the corticosterone rhythm attenuates 5-HT1A autoreceptor function in the rat: Relevance for depression

Abstract

Depression is associated with glucocorticoid abnormalities, in particular a flattening of the diurnalcortisolrhythm. Recent data suggest that an important factor in the aetiology of depression may be a deficit in the function and expression of 5-HT1A receptors, which hasbeen reported in depressed patients. The present study assessed the possibility that this cortisolabnormality is causalin the 5-HT1A receptor deficits. First, a rat modelof flattened glucocorticoid rhythm was developed. Controlled release corticosterone pellets implantedfor 14 days flattened the corticosterone rhythm and maintained levels constant midway between the nadir and zenith levels observed insham-operated rats. Secondly, using microdialysis to assess 5-HT release in the hippocampus, the inhibitory response to 8-OHDPAT wasmeasured to determine the sensitivity of somatodendritic 5-HT1A autoreceptors. Corticosterone treatment was found to induce asignificant attenuation in the response to 8-OHDPAT, indicating functionaldesensitization of somatodendritic 5-HT 1Aautoreceptors.There was no effect of corticosterone treatment on basal extracellular 5-HT levels. The data suggest that the glucocorticoidabnormalities associated with depression may impact on the functioning of 5-HT1A receptors in the brain. These findings suggest thatresolution of cortisolabnormalities may be a valuable target for pharmacotherapy in the treatment of depression. © 2003 American College of Neuropsychopharmacology.