INFLUENCE OF A 1-H IMMOBILIZATION STRESS ON SLEEP STATES AND CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE (CLIP OR ACTH(18-39), PH-ACTH(18-39)) BRAIN CONTENTS IN THE RAT

A 1 h immobilization stress (IS) was imposed to rats at the beginning of the dark period, i.e., when the animals start to be active. The IS was accompanied by an intense polygraphic waking and followed, over 12 h of the dark period, by a significant rebound of slow-wave sleep (SW S, +17%) and paradoxical sleep (PS, +57%). In order to estimate the IS -related changes in the endogenous concentrations of corticotropin-lik e intermediate lobe peptide (CLIP, ACTH(18-39)) and related compounds, a specific radioimmunoassay (RTA) was used. Assays performed in cereb ral biopsies taken from arcuate (AN) and raphe dorsalis (nRD) nuclei l ed to the obtention of 2 main immunoreactive peaks, corresponding to C LIP and its phosphorylated form Ph-CLIP. Just after the end of the IS and within the nRD, Ph-CLIP immunoreactivity increased by about 95%. F our hours later, i.e., when PS rebound was maximal, a 37% increase in Ph-CLIP immunoreactivity was measured in the AN. These observations ha ve never been described before. In the blood, at the end of the restra int, CLIP/ACTH(1-39) total immunoreactivity was increased by 330%. It returned to baseline level 4 h later. Blood concentration of corticost erone was also increased by 56% at the end of the IS and was close to baseline level 4 h later. Data reported here indicate that the IS firs t triggers an increase in Ph-CLIP within the nRD. Since the nRD contai ns sleep permissive components, this increase might be determinant for the SWS and PS rebound induction. The changes observed in the blood a s regards CLIP/ACTH(1-39), total immunoreactivity and corticosterone c oncentration testify to the efficacy of the IS and are part of the con ventional picture accompanying such a situation. Finally, the increase in Ph-CLIP, occurring in the AN 4 h after the end of the restraint, m ight be part of the restorative processes necessary to compensate the stress overshoot. (C) 1997 Elsevier Science B.V.