Abstract In order to determine the effect of chronic and acute stress on muscle mitochondrial metabolism, two strains of rats were selected on the basis of their different hypothalamo-pituitary-adrenal (HPA) axis responses to different stressors [Spontaneous Hypertensive Rats (SHR) and Lewis rats]. For 8 weeks animals were stressed by daily exposure to either a novel environment (SHR: n=16, Lewis: n=16) or forced exercise (SHR: n=16, Lewis: n=16). An unstressed group was left undis- turbed (SHR: n=5, Lewis: n=5). Half of the stressed ani- mals (n=32) were submitted to an acute stress (1-h im- mobilization). The mitochondrial responses of plantaris muscle [cytochrome-c-oxidase (COX), citrate synthase and succinate dehydrogenase activities, the latter two be- ing measured as indices of functional mitochondrial amount] in the presence of different physiological plas- ma corticosterone (CORT) concentrations were ana- lyzed. The novel environment and forced exercise stress induced different levels of plasma CORT which were negatively correlated with the amount of functional mi- tochondria in the plantaris muscle. Therefore, a chronic intermittent stress is able to induce an increase in plasma CORT which may be related to deleterious changes in muscle mitochondrial metabolism. Lastly, the acute stress was not associated with a decrease in functional mitochondria but with an increase in COX activity. This suggests that the relationship between CORT and muscle mitochondrial metabolism depends both on the level and duration of endogenous glucocorticoids exposure. Keywords Chronic stress · Cytochrome-c-oxidase · Glucocorticoids · Immobilization · Mitochondria · Skeletal muscle Introduction Glucocorticoids (GC), hormones released by the adrenal cortex, have numerous homeostatic and stress-response functions. A delicate balance exists between the protec- tive effects of adrenal steroids secreted in response to stressful experiences, and the negative consequences that GC may have for many processes [24]. For example, in skeletal muscles, GC insufficiency leads to debilitating fatigue, myalgia and general muscle weakness [28], whereas excess GC causes muscular atrophy and a decreased rate of muscle protein synthesis [5]. Among several mechanisms leading to muscle wasting in GC-induced myopathy, defects in mitochondria function appear to be involved [21, 22, 34]. Indeed, with the ad- ministration of supraphysiological doses of GC in rat, electron microscopic and biochemical studies have dem- onstrated enlarged mitochondrial volume, decreased numbers of mitochondria, decreased substrate utilization, and uncoupling of oxidative phosphorylation [21]. Stud- ies of the direct effects of GC on mitochondrial metabo- lism have been relatively numerous, consisting of reports describing either the effects following GC treatment of animals in vivo [21, 34] or the in vitro effects of GC on mitochondrial energy metabolism [22, 31]. However, in these studies of synthetic GC (dexamethasone, triamci- nolone, methylprednisolone, etc.), supraphysiological concentrations were widely used [21, 22, 34]. The objective of the present study was to determine the effect of chronic and acute stress on muscle mito- chondrial metabolism and the relationship of the re- sponses observed to the associated changes in plasma corticosterone (CORT) levels. For this purpose, Sponta- M. Duclos ( ✉ ) · F. Chaouloff · P. Mormède Laboratoire Neurogénétique et Stress, INSERM U471, Institut François Magendie, Université Bordeaux II, 33077 Bordeaux Cedex, France e-mail: duclos@vignemale.bordeaux.inserm.fr Tel.: +33-5-57573754, Fax: +33-5-57573752 C. Martin Laboratoire de Physiologie de l’Exercice Musculaire et du Sport, Université Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France M. Malgat · J.-P. Mazat · T. Letellier Laboratoire de Physiologie Mitochondriale, EMIU 9929, Université Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France Pflügers Arch - Eur J Physiol (2001) 443:218–226 DOI 10.1007/s004240100675 ORIGINAL ARTICLE Martine Duclos · Cyril Martin · Monique Malgat Jean-Pierre Mazat · Francis Chaouloff Pierre Mormède · Thierry Letellier Relationships between muscle mitochondrial metabolism and stress-induced corticosterone variations in rats Received: 30 May 2001 / Revised: 27 June 2001 / Accepted: 27 June 2001 / Published online: 27 July 2001 © Springer-Verlag 2001