RESERPINE-INDUCED DECREASE IN TYPE-I AND TYPE-II CORTICOSTEROID RECEPTORS IN NEURONAL AND LYMPHOID-TISSUES OF ADRENALECTOMIZED RATS

The effect of the biogenic amine depleting drug, reserpine, on the concentration of type II corticosteroid receptors (i.e., glucocorticoid receptors) in neuronal (hippocampus, frontal cortex, hypothalamus), lymphoid (circulating lymphocytes, spleen, thymus) and pituitary tissues as well as hippocampal type I (i.e., mineralocorticoid) receptors was examined in adrenal-intact and adrenalectomized (ADX) rats. Reserpine (2 mg/kg) or vehicle was administered to adrenal-intact rats for 2 consecutive days. Following the second injection rats were ADX and sacrificed 24 h later. Reserpine significantly decreased type I and II hippocampal receptors as well as type II receptors in frontal cortex, hypothalamus, lymphocytes and spleen. Since the reserpine-induced decreases in receptor content could be due to reserpine-induced elevations in circulating corticosterone levels, reserpine (2 mg/kg) or vehicle was administered to I -day ADX rats which were then sacrificed 2 days later (i.e., 3 days post ADX). A 1 -day ADX control group was also included. The 3-day ADX regimen produced significant or nearly significant increases in type II receptors in hippocampus, frontal cortex, hypothalamus, lymphocytes and spleen in vehicle-treated rats. Reserpine attenuated the ADX-induced upregulation of type II receptors in hippocampus, frontal cortex, lymphocytes and spleen, but had no effect on the ADX-induced upregulation of type II receptors in the hypothalamus. The ADX-induced increase in hippocampal type I receptors was not affected by reserpine treatment. In a final experiment, reserpine (2 mg/kg) or vehicle was administered immediately after ADX and rats were sacrificed 24 h later in order to assess the effect of reserpine on basal (i.e., nonupregulated) corticosteroid receptor levels in the absence of circulating corticosterone levels. Reserpine decreased type II receptor levels in hippocampus, frontal cortex, lymphocytes, spleen and pituitary. Hippocampal type I receptors were also decreased by reserpine. A correlational analysis of data pooled from all three studies indicated significant positive correlations between type II receptor content in lymphocytes and type II receptor levels in hippocampus, frontal cortex and spleen. These studies indicate that depletion of biogenic amines by reserpine produces differential decreases in type II receptor levels in a variety of tissues under basal and upregulated conditions. The ability of reserpine to produce decreases in type I and II receptors in ADX rats indicates that these receptors can be regulated by an adrenal-independent mechanism. The differential response of ADX-induced upregulated hippocampal type I and II receptors to reserpine provide further evidence that corticosteroid receptors in this structure have distinct regulatory mechanisms. Finally, these studies also suggest that the regulation of neuronal and lymphoid type II receptors are similar and help validate the utility of lymphocyte type II receptor measurements in human disease states, such as depression. © 1990 S. Karger AG, Basel.