Cold water swim (CWS) analgesia in the rat is mediated by the hypothalamo-pituitary-adrenocortical (HPA) axis. An age-dependent increase of CWS-induced analgesia was observed in male Sprague-Dawley young (4 months), adult (15 months) and old (26 months) rats. Acetyl-L-Carnitine (ALCAR) chronically administered (75 mg/kg/daily in drinking water for 8 months) to old rats was able to maintain the stress-dependent response at the same levels as in adult rats. This effect may be explained by ALCAR capability of retarding the age-dependent loss of glucocorticoid receptors in the hippocampus, thus maintaining the glucocorticoid competence of this structure which exerts a negative feedback control over the HPA axis activity.