title: Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis.
abstract: This study aimed at determining the thermoregulatory phenotype of mice lacking transient receptor potential vanilloid-1 (TRPV1) channels. We used Trpv1 knockout (KO) mice and their genetically unaltered littermates to study diurnal variations in deep body temperature (T(b)) and thermoeffector activities under basal conditions, as well as thermoregulatory responses to severe heat and cold. Only subtle alterations were found in the basal T(b) of Trpv1 KO mice or in their T(b) responses to thermal challenges. The main thermoregulatory abnormality of Trpv1 KO mice was a different pattern of thermoeffectors used to regulate T(b). On the autonomic side, Trpv1 KO mice were hypometabolic (had a lower oxygen consumption) and hypervasoconstricted (had a lower tail skin temperature). In agreement with the enhanced skin vasoconstriction, Trpv1 KO mice had a higher thermoneutral zone. On the behavioral side, Trpv1 KO mice preferred a lower ambient temperature and expressed a higher locomotor activity. Experiments with pharmacological TRPV1 agonists (resiniferatoxin and anandamide) and a TRPV1 antagonist (AMG0347) confirmed that TRPV1 channels located outside the brain tonically inhibit locomotor activity. With age (observed for up to 14 months), the body mass of Trpv1 KO mice exceeded that of controls, sometimes approaching 60 g. In summary, Trpv1 KO mice possess a distinct thermoregulatory phenotype, which is coupled with a predisposition to age-associated overweight and includes hypometabolism, enhanced skin vasoconstriction, decreased thermopreferendum, and hyperkinesis. The latter may be one of the primary deficiencies in Trpv1 KO mice. We propose that TRPV1-mediated signals from the periphery tonically suppress the general locomotor activity.
authors.affiliation: Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
authors.forename: Andras
authors.initials: A
authors.lastname: Garami
authors.forename: Eszter
authors.initials: E
authors.lastname: Pakai
authors.forename: Daniela L
authors.initials: DL
authors.lastname: Oliveira
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Steiner
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Wanner
authors.forename: M Camila
authors.initials: MC
authors.lastname: Almeida
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Lesnikov
authors.forename: Narender R
authors.initials: NR
authors.lastname: Gavva
authors.forename: Andrej A
authors.initials: AA
authors.lastname: Romanovsky
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001831:Body Temperature / Q000235:genetics; D001833:Body Temperature Regulation / Q000235:genetics*; D003080:Cold Temperature; D004224:Diterpenes / Q000494:pharmacology; D063388:Endocannabinoids; D005260:Female; D006358:Hot Temperature; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009483:Neuropsychological Tests; D050177:Overweight / Q000378:metabolism*; D010101:Oxygen Consumption; D010641:Phenotype; D016133:Polymerase Chain Reaction; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012867:Skin / Q000098:blood supply; D012881:Skin Temperature / Q000235:genetics; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D014661:Vasoconstriction
chemical_list: D000178:Acrylamides; D001095:Arachidonic Acids; D004224:Diterpenes; D063388:Endocannabinoids; C521703:N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylamide; D053284:Polyunsaturated Alkamides; D011725:Pyridines; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C024353:resiniferatoxin; C078814:anandamide