beta-endorphin and Hypothermia

Topics: Animals; beta-Endorphin; Body Temperature; Body Temperature Regulation; Dose-Response Relationship, Drug; Drug Tolerance; Endorphins; Enkephalin, Methionine; Fever; Hypothermia; Mice; Morphine; Narcotic Antagonists; Narcotics; Rats; Receptors, Opioid; Temperature

We have shown previously that intracerebroventricular (icv) injection of naloxone (a non-selective opioid receptor antagonist) or naloxonazine (a selective μ1-opioid receptor antagonist) at the maintenance phase of hibernation arouses Syrian hamsters from hibernation. This study was designed to clarify the role of β-endorphin (an endogenous μ-opioid receptor ligand) on regulation of body temperature (T(b)) during the maintenance phase of hibernation. The number of c-Fos-positive cells and β-endorphin-like immunoreactivity increased in the arcuate nucleus (ARC) after hibernation onset. In contrast, endomorphin-1 (an endogenous μ-opioid receptor ligand)-like immunoreactivity observed on the anterior hypothalamus decreased after hibernation onset. In addition, hibernation was interrupted by icv injection of anti-β-endorphin antiserum at the maintenance phase of hibernation. The mRNA expression level of proopiomelanocortin (a precursor of β-endorphin) on ARC did not change throughout the hibernation phase. However, the mRNA expression level of prohormone convertase-1 increased after hibernation onset. [D-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO, a selective μ-opioid receptor agonist) microinjection into the dorsomedial hypothalamus (DMH) elicited the most marked T(b) decrease than other sites such as the preoptic area (PO), anterior hypothalamus (AH), lateral hypothalamus (LH), ventromedial hypothalamus and posterior hypothalamus (PH). However, microinjected DAMGO into the medial septum indicated negligible changes in T(b). These results suggest that β-endorphin which synthesizes in ARC neurons regulates T(b) during the maintenance phase of hibernation by activating μ-opioid receptors in PO, AH, VMH, DMH and PH.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Body Temperature Regulation; Brain Chemistry; Cell Count; Central Nervous System; Cricetinae; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Hibernation; Hypothalamus; Hypothermia; Immunohistochemistry; Injections, Intraventricular; Mesocricetus; Oligopeptides; Polymerase Chain Reaction; Proprotein Convertase 1; Proto-Oncogene Proteins c-fos; Receptors, Opioid, mu

Regulations of hormonal stress responses entail the initiation, amplitude and termination of the reaction, as well as its integration with other stress response systems. This study investigates the role of endogenous opioids in the regulation and integration of behavioral, thermal and hormonal stress responses, as these neuromodulators and their receptors are expressed in limbic structures responsible for stress responses. For this purpose, we subjected mice with selective deletion of beta-endorphin, enkephalin or dynorphin to the zero-maze test, a mildly stressful situation, and registered behaviors and stress hormone levels. Behavioral stress reactivity was assessed using zero-maze, light-dark and startle-reactivity paradigms. Animals lacking enkephalin displayed increased anxiety-related behavioral responses in each three, dynorphin knockouts in two models, whereas the responses of beta-endorphin knockouts indicated lower anxiety level in the zero-maze test. All knockout strains showed marked changes in hormonal stress reactivity. Increase in ACTH level after zero-maze test situation, unlike in wild type animals, failed to reach the level of significance in Penk1(-/-) and Pdyn(-/-) mice. Corticosterone plasma levels rapidly increased in all strains, with a lower peak response in knockouts. In wild-type and beta-endorphin-deficient mice, corticosterone levels returned to baseline within 60min after stress exposure. In contrast, mice lacking dynorphin and enkephalin showed longer-lasting elevated corticosterone levels, indicating a delayed termination of the stress reaction. Importantly, the behavioral and hormonal responses correlated in wild-type but not in knockout mice. Hyperthermia elicited by stress was reduced in animals lacking dynorphin and absent in Penk1(-/-) mice, despite of the heightened behavioral anxiety level of these strains. These results demonstrate an important role on the endogenous opioid system in the integration of behavioral and hormonal stress responses.

Topics: Adrenocorticotropic Hormone; Amygdala; Analysis of Variance; Animals; Anxiety; beta-Endorphin; Corticosterone; Dynorphins; Enkephalins; Exploratory Behavior; Hypothermia; Limbic System; Male; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Knockout; Opioid Peptides; Paraventricular Hypothalamic Nucleus; Protein Precursors; Proto-Oncogene Proteins c-fos; Reflex, Startle; Stress, Psychological; Time Factors

Previous studies have shown that the same stressor, depending on intensity, controllability, or duration, can have different effects on the immune system. The purpose of this study was to determine the effect of 10- and 20-min rotation on natural killer (NK) cell activity and also to establish if changes in body temperature, proinflammatory cytokine (IL-1beta, IL-6, and TNF-alpha) levels, and proopiomelanocortin (POMC)-derived peptide (ACTH and beta-endorphin) levels parallel the changes in NK cell activity in mice. We found that 10-min rotation significantly increased NK cell activity as compared to both the control (home cage) group and the 20-min-rotation group, while NK cell activity in the 20-min group was not significantly changed compared to the control group. Both 10 and 20 min of rotational stress decreased body temperature and induced significant changes in the proinflammatory cytokine and POMC-derived peptide levels as compared to the control group. The pattern of proinflammatory cytokine expression was quite different between the 10- and 20-min rotation groups. All three proinflammatory cytokines were expressed sequentially (at 0 h after rotation TNF-alpha, at 6 h IL-1beta and IL-6, and at 24 h IL-6) in the 10-min rotation group, while the 20-min rotation group had a small increase in IL-1beta (6.7 +/- 1.8 pg/ml) at 0 h and increased levels of IL-6 at 6 and 24 h. There was a dissociation of ACTH and beta-endorphin expression in both groups resulting in significantly more beta-endorphin (p < 0.05) in the 10-min group at 6 h and significantly more ACTH (p < 0.04) in the 20-min group at 6 h. IL-1beta and beta-endorphin have both been shown to have a direct stimulatory effect on NK cell activity. Therefore, we suspect that the significant increase in both IL-1beta and beta-endorphin at 6 h in the 10-min-rotation group may be involved in the increased NK cell activity observed at 24 h in the 10-min-rotation group.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Cytotoxicity, Immunologic; Female; Hypothermia; Inflammation; Interleukin-1; Interleukin-6; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Neuroimmunomodulation; Rotation; Stress, Physiological; Tumor Necrosis Factor-alpha

1. The effects of intravenous (i.v.) morphine on adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-END), total catecholamines (CA) and histamine (HIS) plasma concentrations, were determined in anaesthetized dogs at 30 degrees C and 37 degrees C. 2. Hypothermia initially increased CA levels by 29%, but the values returned to baseline after 2 h. Morphine (1 mg/kg, i.v.) produced a significant decrease in CA both at 37 degrees C and 30 degrees C (34% and 54%, respectively). Subsequent administration of naloxone (1 mg/kg, i.v.) significantly increased CA levels in both groups. 3. Hypothermia per se had no effect on ACTH, beta-END, and HIS concentrations. Morphine produced a significant increase in pituitary hormones and HIS, in hypothermic but not in normothermic animals. Morphine concentrations were significantly higher at 30 degrees C during the first 45 min. 4. The results suggest that the effects of morphine on hormonal and histamine release observed at 30 degrees C are concentration-dependent and related to changes in morphine pharmacokinetics.

Topics: Adrenocorticotropic Hormone; Anesthesia; Animals; beta-Endorphin; Catecholamines; Dogs; Histamine; Histamine Release; Hormones; Hypothermia; Morphine; Naloxone; Time Factors

Neurotensin (NT) differentially altered ethanol-induced anesthesia as measured by duration of loss of righting response or by blood ethanol levels producing loss of righting response in mice (LS and SS) which were selectively bred for differences in response to ethanol. At doses of 5-500 ng i.c.v., NT increased ethanol sensitivity in SS mice, but not in LS mice, as measured by blood ethanol concentrations at loss of righting response. At higher doses, 0.5-10 micrograms i.c.v., NT enhanced the sensitivity of both SS and LS mice to ethanol-induced anesthesia. The hypothermic effect of ethanol determined at loss of righting response was not altered in either LS or SS mice at low doses of NT, but at higher doses NT enhanced ethanol-induced hypothermia in both lines of mice. The altered anesthetic sensitivity was specific for ethanol in that NT did not alter pentobarbital-induced sleep time in either LS or SS mice and halothane anesthesia was altered slightly only in LS mice. NT analogues, N-acetyl-NT8-13, and [D-Trp11]-NT but not NT1-8 enhanced the anesthetic action of ethanol in SS mice. Bombesin, cholecystokinin sulfate, substance P, [D-Trp8, D-Cys14]-somatostatin and corticotropin releasing hormone (CRF) were not effective in enhancing ethanol-induced anesthesia in LS or SS mice. CRF appeared to decrease ethanol sensitivity in LS but not in SS mice. Beta-Endorphin (beta-END) markedly increased the ethanol sensitivity of SS and to a lesser extent of LS mice at relatively high doses, e.g. 0.5-1.0 micrograms i.c.v. The results of the present study indicate that differences in brain sensitivity of LS and SS mice to ethanol may be mediated by genetic differences in NT systems. Likewise, NT, and probably beta-endorphin, may interact with other neurochemical processes that are involved in the mechanism of ethanol-induced anesthesia and that differ genetically in LS and SS mice.

Topics: Animals; beta-Endorphin; Brain; Endorphins; Ethanol; Hypothermia; Male; Mice; Mice, Mutant Strains; Neuropeptides; Neurotensin; Sleep

The effects of the three peptides neurotensin, beta-endorphin, and bombesin on ethanol-induced behaviors were studied in mice. Intracisternal administration of these peptides to mice prolonged the duration of sleep induced by ethanol (5.2 g/kg). Neurotensin and beta-endorphin also enhanced ethanol-induced hypothermia. None of the peptides, when administered alone, produced sleep. However, all three compounds impaired the aerial righting reflex and induced sleep when followed by an IP dose of ethanol (3.5 g/kg), which alone did not induce sleep. These results, taken together with previous findings, suggest that neuropeptides may be involved in the complex mechanisms of action of ethanol on the CNS.

Topics: Animals; Behavior, Animal; beta-Endorphin; Bombesin; Endorphins; Ethanol; Hypothermia; Male; Mice; Mice, Inbred Strains; Naloxone; Neurotensin; Peptides; Reflex; Sleep; Thyrotropin-Releasing Hormone

Topics: Animals; beta-Endorphin; Bombesin; Drug Synergism; Endorphins; Ethanol; Hypnotics and Sedatives; Hypothermia; Male; Mice; Neurotensin; Pentobarbital; Peptides