Is there tonic activity in the endogenous opioid systems? A c-Fos study inthe rat central nervous system after intravenous injection of naloxone or naloxone-methiodide

This study examined the possibility that a tonic activity in the endogenous opioid systems (EO systems) exists in animals under normal conditions. In a first set of experiments, concurrent changes in behavioral responses and in the numbers of c-Fos-like immunoreactive (Fos-LI) neurons in 58 structur es of the brain and lumbosacral spinal cord were analyzed in rats after sys temic administration of the opioid antagonist naloxone (NAL; 2 mg/kg). Poss ible roles of the EO systems were inferred from changes in the numbers of F os-LI neurons between normal rats that received either NAL or the same volu me of saline. Free-floating sections were processed immunohistochemically f or c-Fos protein using standard avidin-biotin complex methods. After NAL, t he numbers of Fos-LI neurons were significantly increased in the area postr ema; in the caudal, intermediate, and rostral parts of the nucleus tractus solitarii; in the rostral ventrolateral medulla; in the Kolliker-Fuse nucle us; in the supramammillary nucleus; and in the central nucleus of the amygd ala. In a second set of experiments examining changes in c-Fos expression i n the latter structures, similar increases were found after NAL but not aft er an equimolar dose of NAL-methiodide, a preferential, peripherally acting opioid receptor antagonist. Therefore, Fos-LI was likely triggered after b lockade of central opioid receptors, but not peripheral opioid receptors, r eleasing neurons from EO system-mediated inhibition. The results of this st udy suggest the existence of a tonic activity of the EO systems exerted on a restricted number of brain regions in normal rats. This tonic activity of the EO systems may control part of the neural networks involved in cardior espiratory functions and in emotional and learning processes. (C) 2000 Wile y-Liss, Inc.