Hibernation “trigger”: Opioid-like inhibitory action on brain function of the monkey

doi:10.1016/0091-3057(82)90132-0

Pharmacology Biochemistry and Behavior

Volume 17, Issue 6, December 1982, Pages 1271-1274

https://doi.org/10.1016/0091-3057(82)90132-0 Get rights and content

Abstract

A hibernation “trigger” factor derived from the blood of the hibernating woodchuck acts to suppress vital physiological processes in the primate. When infused into the cerebral ventricle of the conscious monkey, the factor induced hypothermia, behavioral depression, bradycardia and aphagia. The opiate antagonists, naloxone and naltrexone, either reverse of retard these behavioral and physiological signs. We hypothesize that the “trigger” molecule is an endogenous opioid-like peptide which may be unique to the hibernator. Moreover, the non-hibernating primate apparently possesses receptor sites in the brain that are capable of responding to this potent molecule.

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Citation Excerpt :
Pharmacological activation of different opioid receptors have been shown to modulate the degree of thermal sensitivity in POA neurons in slices (Xin and Blatteis, 1992; Yakimova et al., 1998, 1996), and to induce hypothermia in rats (Yakimova and Pierau, 1999). On these bases, it is indeed interesting that naloxone can arouse the hamster from torpor (Margules et al., 1979), since endogenous opioid has been reported to play a key role in regulating hibernation (Beckman and Llados-Eckman, 1985; Cui et al., 1993; Oeltgen et al., 1982; Tamura et al., 2012). An interesting physiological state characterized by the loss of the intrinsic thermosensitivity of the POA warm and cold sensitive neurons is REM (Parmeggiani, 1986).
In mammals, torpor/hibernation is a state that is characterized by an active reduction in metabolic rate followed by a progressive decrease in body temperature. Torpor was successfully mimicked in non-hibernators by inhibiting the activity of neurons within the brainstem region of the Raphe Pallidus, or by activating the adenosine A1 receptors in the brain. This state, called synthetic torpor, may be exploited for many medical applications, and for space exploration, providing many benefits for biological adaptation to the space environment, among which an enhanced protection from cosmic rays. As regards the use of synthetic torpor in space, to fully evaluate the degree of physiological advantage provided by this state, it is strongly advisable to move from Earth-based experiments to ‘in the field’ tests, possibly on board the International Space Station.
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In attempts to replicate this finding, intracerebroventricular injection of serum from hibernating woodchucks containing ‘hibernation-induction trigger (HIT)’ was shown to make primates hypothermic, bradycardic and hypophagic. Although metabolism was not measured, the thought was that HIT had induced metabolic depression [45]. HIT was thought to mediate its effects by an independent effect on endogenous opioids [46].
Interest in mimicking hibernating states has led investigators to explore the biological mechanisms that permit hibernating mammals to survive for months at extremely low ambient temperatures, with no food or water, and awaken from their hibernation without apparent organ injury. Hibernators have evolved mechanisms to adapt to dramatic reductions in core body temperature and metabolic rate, accompanied by prolonged periods without nutritional intake and at the same time tolerate the metabolic demands of arousal. This review discusses the inherent resilience of hibernators to kidney injury and provides a potential framework for new therapies targeting ex vivo preservation of kidneys for transplantation.
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Background. Opioid receptor agonists are involved in ischemic preconditioning and natural hibernation. The aim of this study was to determine whether pretreatment with d-Ala2-Leu5-enkephalin or morphine confers cardioprotection in large mammalian hearts. We assessed myocardial functional recovery and global energy metabolism after ischemic cold storage.
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Hibernation “trigger”: Opioid-like inhibitory action on brain function of the monkey

Abstract

Life Sci.

J. biol. Chem.

Brain Res. Bull.

Comp. Biochem. Physiol.

Comp. Biochem. Physiol.

Physical dependence on morphine fails to develop during the hibernating state

Science