DOSE-DEPENDENT SUPPRESSION OF ADRENOCORTICAL ACTIVITY WITH METYRAPONE- EFFECTS ON EMOTION AND MEMORY

Different levels of circulating corticosterone are considered to produ ce different emotional states and effects on learning and memory. The purpose of the present study was to use different doses of the 11-beta -hydroxylase inhibitor metyrapone to produce dose-dependent inhibition of the synthesis of corticosterone and examine the consequences of th at on several cognitive and emotional parameters. Systemic (SC) inject ions of metyrapone (25 or 50 mg/kg) dose-dependently suppressed increa ses in plasma concentrations of corticosterone induced by spatial trai ning in a water maze, but did not affect plasma corticosterone levels in non-stressed rats. Treatment with the higher and lower dose of mety rapone also differentially affected behavioral measures of emotion and memory. Administration of 50 mg/kg, but not 25 mg/kg, of metyrapone i mpaired acquisition performance in the spatial water maze task. Both d oses of metyrapone impaired retention. The impairment in retention was attenuated by dexamethasone (0.3 mg/kg) given systemically immediatel y after training, but not by corticosterone (0.3 mg/kg). During the ex posure to a conditioned stressor of inescapable footshock, the higher, but not the lower dose of metyrapone attenuated fear induced immobili ty. In contrast, the lower, but not the higher dose attenuated the anx iety state in an elevated plus-maze in a novel environment immediately after exposure to the conditioned stressor. It is suggested that emot ion, learning, and memory are differentially affected by the different doses of metyrapone due to interference with different types of adren al steroid receptors and consequent induction of various corticosteron e receptor states. (C) 1997 Elsevier Science Ltd.