Lower core body temperature and attenuated nicotine-induced hypothermic response in mice lacking the β4 neuronal nicotinic acetylcholine receptor subunit

Diverse physiological and pathological effects of nicotine, including the alteration of body temperature, are presumably mediated by neuronal nicotinic acetylcholine receptors (nAChR). Previous studies have suggested the involvement of distinct nAChR subunits in nicotine-induced thermoregulation. We studied genetically manipulated knockout mice lacking the alpha 7, alpha 5 or beta 4 subunit genes, in order to assess the effects of subunit deficiency on temperature regulation. Using a telemetry system, core body temperature was monitored continuously prior to and following nicotine administration in mutant mice and in wild-type littermates. Mice lacking in the beta 4 nAChR subunit gene had significantly lower baseline core body temperature than all other mouse strains studied. beta 4 null mice also demonstrated a reduced nicotine-induced hypothermic response and impaired desensitization following repeat nicotine exposure. These findings suggest the involvement of the beta 4 nAChR subunit in both core body temperature homeostasis and nicotine-elicited thermo-alterations in mice. (c) 2005 Elsevier Inc. All rights reserved.