Selective down-regulation of hippocampal glucocorticoid receptors during opiate withdrawal.

The effects of opiate dependence and antagonist-precipitated withdrawal on glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA levels in the rat brain were studied. Rats were allocated to one of four groups that differed in terms of type of drug pretreatment (morphine pellet versus placebo pellet) and type of injection on test (naloxone versus no injection). Injection of naloxone precipitated a somatic withdrawal syndrome among morphine pretreated rats. In situ hybridization histochemistry revealed a potent down-regulation of hippocampal GR mRNA 4 h after injection of naloxone. Levels of GR mRNA in the amygdala and hypothalamus were unchanged. Hippocampal MR mRNA levels from these same animals were unchanged. By contrast, neither chronic morphine exposure nor injection of naloxone in morphine naive animals affected GR or MR mRNA levels. These results show that during opiate dependence the levels of hippocampal GR mRNA are more sensitive to episodes of withdrawal than to chronic drug exposure and are consistent with an increased vulnerability to stress during opiate dependence.