title: The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat.
abstract: The possibility of inducing a suspended animation state similar to natural torpor would be greatly beneficial in medical science, since it would avoid the adverse consequence of the powerful autonomic activation evoked by external cooling. Previous attempts to systemically inhibit metabolism were successful in mice, but practically ineffective in nonhibernators. Here we show that the selective pharmacological inhibition of key neurons in the central pathways for thermoregulatory cold defense is sufficient to induce a suspended animation state, resembling natural torpor, in a nonhibernator. In rats kept at an ambient temperature of 15°C and under continuous darkness, the prolonged inhibition (6 h) of the rostral ventromedial medulla, a key area of the central nervous pathways for thermoregulatory cold defense, by means of repeated microinjections (100 nl) of the GABA(A) agonist muscimol (1 mm), induced the following: (1) a massive cutaneous vasodilation; (2) drastic drops in deep brain temperature (reaching a nadir of 22.44 ± 0.74°C), heart rate (from 440 ± 13 to 207 ± 12 bpm), and electroencephalography (EEG) power; (3) a modest decrease in mean arterial pressure; and (4) a progressive shift of the EEG power spectrum toward slow frequencies. After the hypothermic bout, all animals showed a massive increase in NREM sleep Delta power, similarly to that occurring in natural torpor. No behavioral abnormalities were observed in the days following the treatment. Our results strengthen the potential role of the CNS in the induction of hibernation/torpor, since CNS-driven changes in organ physiology have been shown to be sufficient to induce and maintain a suspended animation state.
authors: Department of Biomedical and NeuroMotor Sciences, Alma Mater Studiorum-University of Bologna, 40126 Bologna Italy. matteo.cerri@unibo.it
authors: Matteo
authors: M
authors: Cerri
authors: Marco
authors: M
authors: Mastrotto
authors: Domenico
authors: D
authors: Tupone
authors: Davide
authors: D
authors: Martelli
authors: Marco
authors: M
authors: Luppi
authors: Emanuele
authors: E
authors: Perez
authors: Giovanni
authors: G
authors: Zamboni
authors: Roberto
authors: R
authors: Amici
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D002404:Catheterization; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D003080:Cold Temperature; D004569:Electroencephalography; D004576:Electromyography; D018755:GABA Agonists / Q000494:pharmacology; D006605:Hibernation / Q000502:physiology*; D007035:Hypothermia / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017694:Rewarming; D012890:Sleep / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
chemical_list: D018755:GABA Agonists; D009118:Muscimol