Lower core body temperature and attenuated nicotine-induced hypothermic response in mice lacking the beta4 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 alpha7, alpha5 or beta4 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 beta4 nAChR subunit gene had significantly lower baseline core body temperature than all other mouse strains studied. beta4 null mice also demonstrated a reduced nicotine-induced hypothermic response and impaired desensitization following repeat nicotine exposure. These findings suggest the involvement of the beta4 nAChR subunit in both core body temperature homeostasis and nicotine-elicited thermo-alterations in mice.
Sack
Ram
R
The Genetics Institute, Tel-Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel.
Gochberg-Sarver
Alona
A
Rozovsky
Uri
U
Kedmi
Merav
M
Rosner
Serena
S
Orr-Urtreger
Avi
A
D000818:Animals; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects; D005838:Genotype; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010507:Periodicity; D011978:Receptors, Nicotinic / Q000145:classification / Q000172:deficiency* / Q000502:physiology; D013686:Telemetry / Q000379:methods
C486720:Chrnb4 protein, mouse; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine