Opioids and hibernation. II. Effects of kappa opioid U69593 on induction of hibernation in summer-active ground squirrels by “hibernation induction trigger” (HIT)

Oeltgen, Peter R.; Welborn, John R.; Nuchols, Paula A.; Spurrier, Wilma A.; Bruce, David S.; Su, Tsung‐Ping

doi:10.1016/0024-3205(87)90529-7

Cited by 40 publications

(12 citation statements)

References 13 publications

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“…Liganddriven mechanisms controlling hibernation have been investigated for more than 30 years (22,38,48). Some of the proposed molecules include circulating hormones such as vasopressin (21), and neurotransmitters, such as serotonin (45), histamine (61), and GABA (49).…”

Section: Discussionmentioning

confidence: 99%

Hibernation induces pentobarbital insensitivity in medulla but not cortex

Hengen¹,

Behan²,

Carey³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Hengen KB, Behan M, Carey HV, Jones MV, Johnson SM. Hibernation induces pentobarbital insensitivity in medulla but not cortex. Am J Physiol Regul Integr Comp Physiol 297: R1028-R1036, 2009. First published August 12, 2009 doi:10.1152/ajpregu.00239.2009.-The 13-lined ground squirrel (Ictidomys tridecemlineatus), a hibernating species, is a natural model of physiological adaption to an extreme environment. During torpor, body temperature drops to 0 -4°C, and the cortex is electrically silent, yet the brain stem continues to regulate cardiorespiratory function. The mechanisms underlying selective inhibition in the brain during torpor are not known. To test whether altered GABAergic function is involved in regional and seasonal differences in neuronal activity, cortical and medullary slices from summer-active (SA) and interbout aroused (IBA) squirrels were placed in a standard in vitro recording chamber. Silicon multichannel electrodes were placed in cortex, ventral respiratory column (VRC), and nucleus tractus solitarius (NTS) to record spontaneous neuronal activity. In slices from IBA squirrels, bath-applied pentobarbital sodium (300 M) nearly abolished cortical neuronal activity, but VRC and NTS neuronal activity was unaltered. In contrast, pentobarbital sodium (300 M) nearly abolished all spontaneous cortical, VRC, and NTS neuronal activity in slices from SA squirrels. Muscimol (20 M; GABAA receptor agonist) abolished all neuronal activity in cortical and medullary slices from both IBA and SA squirrels, thereby demonstrating the presence of functional GABAA receptors. Pretreatment of cortical slices from IBA squirrels with bicuculline (100 M; GABAA receptor antagonist) blocked pentobarbital-dependent inhibition of spontaneous neuronal activity. We hypothesize that GABAA receptors undergo a seasonal modification in subunit composition, such that cardiorespiratory neurons are uniquely unaffected by surges of an endogenous positive allosteric modulator.␥-aminobutyric acid receptors; ventral respiratory groups; nucleus tractus solitarius; respiratory control DURING WINTER HIBERNATING, mammals enter a state of torpor, defined by dramatically reduced metabolic and physical activity and low body temperature (T b ). The torpid state is interrupted periodically by interbout arousals to euthermia (T b ϭ 37°C) that generally last less than 24 h (3, 8). During torpor bouts, T b drops to just above ambient temperature and can approach 0°C, and respiration and heart rate drop as low as 1% of euthermic values (39,71). Neurons in the cortex, hippocampus, and thalamus are electrically silent in torpid hibernators (14, 67). Despite evidence for global forebrain depression, torpid hibernators maintain a robust, neuronally regulated cardiorespiratory output (37,25,41), suggesting that respiratoryand cardiovascular-related neurons in the brain stem remain active. The mechanisms that selectively depress the forebrain during hibernation are not well understood and may contribute to hibernators' unique ability to survive ischemia, hyp...

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Section: Discussionmentioning

confidence: 99%

Hibernation induces pentobarbital insensitivity in medulla but not cortex

Hengen¹,

Behan²,

Carey³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Morphine and morphiceptin, relatively selective for mu opioid receptors, were low in efficacy in inducing hibernation [18]. Similarly, dynorphin and U-69593, two selective kappa opioids, were also low in efficacy in inducing hibernation in summer-active ground squirrels [17,18]. However, morphine, morphiceptin, dynorphin, or U-69593, when coadministered with HIT, can block the HIT-induced hibernation [18].…”

Section: Sumentioning

confidence: 95%

Delta Opioid Peptide[D- Ala2,D-Leu5]Enkephalin Promotes Cell Survival

Su¹

2000

J Biomed Sci

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By studying the hibernation in ground squirrels, a protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Further purification of HIT yielded an 88-kD peptide that is enriched in winter hibernator. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Delta opioid [D-Ala²,D-Leu⁵]enkephalin (DADLE) also induced hibernation. HIT and DADLE were found to prolong survival of peripheral organs preserved en bloc or as a single preparation. These organs include the lung, the heart, liver and kidney. DADLE also promotes survival of neurons in the central nervous system. Methamphetamine (METH) is known to cause destruction of dopaminergic (DA) terminals in the brain. DADLE blocked and reversed the DA terminal damage induced by METH. DADLE acted against this effect of METH at least in part by attenuating the mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. DADLE also blocked the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In PC12 cells, DADLE blocked the cell death caused by serum deprivation in a naltrexone-sensitive manner. Thus, DADLE, and by extension the endogenous delta opioid peptides and delta opioid receptors, may play an important role in organ and neuronal survival. Here, critical developments concerning these fascinating cell protective properties of DADLE are reviewed.

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“…A role for opioids in hibernation had been proposed [55], and indeed hypothermia and hypophagia in monkeys caused by icv administration of serum albumin fraction from WC [56] was blocked by the non-selective opiate antagonists naltrexone and naloxone [54]. Tests of more specific agonists suggested that the δ−opioid receptor was involved in hibernation [57].…”

Section: The Search For a "Hibernation Induction Trigger" Leads Tmentioning

confidence: 97%