CCK-8 induces fever-like regulated hyperthermia and symptoms of sickness behavior in mice: A biotelemetric study E. Pe ´ terva ´ ri a , M. Balasko ´ a , M. Solyma ´r a , A. Pa ´ rniczky a , M. Sze ´ kely a , Z. Szele ´ nyi a,b,n a Department of Pathophysiology and Gerontology, Faculty of Medicine, University of Pe ´cs, Pe ´cs, Hungary b Department of Nursing Sciences, Faculty of Health Sciences, University of Pe´cs, Pe ´cs, Hungary article info Available online 7 August 2011 Keywords: CCK-8 i.c.v. infusion Mice Fever Sickness behavior Biotelemetry abstract In earlier studies it has been found that rats respond to intracerebroventricular (i.c.v.) injection of cholecystokinin-octapeptide (CCK-8) with a febrile response characterized by rises of heat production and core temperature together with tail-skin vasoconstriction mediated by CCK2 receptors. Biotele- metric investigations of the same species have additionally shown that CCK-induced fever is accompanied by decreased locomotor activity. Similar data for mice have not been reported so far. In the present studies C57BL/6 mice were infused i.c.v. for 3 days with CCK-8 to see effects on body core temperature, locomotor activity, food intake and body weight. Biotelemetric monitoring disclosed a rise in daylight core temperature and a fall of night-time locomotor activity both lasting beyond the time of i.c.v. infusions. Food intake was suppressed only during infusion, while a significant decrease of body weight was sustained after the end of CCK-8 infusion. It is concluded that similar to rats mice also respond to i.c.v. infusion of CCK-8 with a fever-like (regulated) hyperthermia and some components of sickness behavior as measured by biotelemetry, and thus a CCK-mediated mechanism may contribute to fever genesis also in mice. & 2011 Elsevier Ltd. All rights reserved. 1. Introduction Evidence for the possible role of CNS peptides in thermoregu- lation, in general, and in fever genesis, in particular, has been sought during the last couple of decades in various species (for a review see Sze ´ kely and Szele ´ nyi, 2005). Among the neuropeptides tested for their relevance in the regulation of energy balance, different forms of cholecystokinin (CCK) have proved to be effective as appetite suppressants either when administered peripherally or centrally (Daun and McCarthy, 1993; Gibbs et al., 1973). Forms of abnormal energy balance, such as hypothermia or regulated hyperthermia (fever-like response) may result from changes in CCK-mediated mechanisms either in connection to or independent of alterations of food intake behavior. In fact, among the thermoregulatory abnormalities just mentioned, regulated hyperthermia resembling fever associated with infectious agents (Gordon, 1983) may have a special place as a centrally induced phenomenon affecting body core tempera- ture, food intake behavior and general physical activity, a triad (high core temperature, anorexia and inactivity) known to be an important set of components of sickness behavior, all of which are involved in changes of body energy balance (Hart, 1988). Indeed, the role of CCK-8 in the mediation of endotoxin fever has been raised in rat studies some two decades ago, after some sporadic data had already been published on rise of core temperature after CCK administration in experiments carried out in other species (Szele ´ nyi et al., 1994; Sze ´ kely et al., 1994). In particular, in slightly restrained conscious female rats, CCK-8 injected intracerebroventricularly (i.c.v.) induced a short-latency rise in core temperature that was accompanied by skin vasocon- striction in case of an initial vasodilation (at thermoneutrality) or by a rise in heat production when there was an initial vasocon- striction (in a subthermoneutral environment). Additionally, cen- tral administration of a CCK2 receptor antagonist suppressed experimental endotoxin fever in rats. In a more recent biotele- metric study carried out in unrestrained female rats, CCK-8 was infused i.c.v. for 7 days to see if general activity, a behavioral parameter, could change in a way corresponding to fever-like regulated hyperthermia (Szele ´ nyi et al., 2004). According to these expectations, an i.c.v. infusion of CCK-8 induced a rise in body core temperature during the day and at higher doses even the night-time maxima were increased. Along with rises of body temperature there was a reduction of general activity resembling the inactivity of sickness behavior. To extend the idea of a fever-like regulated effect of centrally administered CCK peptides, other species have to be studied. Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jtherbio Journal of Thermal Biology 0306-4565/$ - see front matter & 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jtherbio.2011.07.013 n Corresponding author at: Department of Pathophysiology and Gerontology, Faculty of Medicine, H-7624 Pe ´ cs, Szigeti Str. 12, Hungary. Tel.: þ36 72 536246; fax: þ36 72 536247. E-mail address: zoltan.szelenyi@aok.pte.hu (Z. Szele ´ nyi). Journal of Thermal Biology 37 (2012) 297–301