Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Nociceptin (Orphanin FQ) is a newly discovered endogenous heptadecapeptide substrate for the opioid-receptor-like 1 receptor, a G protein coupled receptor that bears striking amino acid sequence homology to opiate receptors. In rats, intrathecal (i.t.) administration of nociceptin is without effect on basal thresholds for responsiveness to electric foot shock. However, during either late gestation or its hormonal simulation, when nociceptive thresholds are elevated by approximately 70%, i.t. nociceptin substantially attenuates jump thresholds in a dose-dependent fashion. This hypoalgesic effect of nociceptin is not limited to attenuating the gestational or sex steroid-induced increment in pain thresholds. Following the highest i.t. dose of nociceptin employed (20 nmol), the gestational or sex steroid-induced increment in jump thresholds is not only abolished but a significant hyperalgesia is observed. These results underscore the importance of the hormonal milieu to nociceptin hypoalgesic sensitivity. The potential contribution of spinal nociceptive pathways that utilize nociceptin to the etiology of extraordinary painful pregnancy and labor should not be ignored.     

Role of vagus nerves in antiarrhythmic effect of DAGO in acute myocardial ischemia

Acute experiments on cats show that DAGO, a selective μ-opiate receptor agonist, elicits a pronounced antiarrhythmic effect in ischemia-induced arrhythmias. The protective effect of DAGO is observed only under conditions of intact parasympathetic innervation of the heart and apparently depends on then. vagus activity and stimulating effect of DAGO on acetylcholine release. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 377–379, October, 1997     

Diabetes alters μ and κ opioid binding in rat brain regions: comparison with effects of food restriction

Diabetic rats display changes in opioid pharmacology and brain regional levels of opioid peptides and prodynorphin mRNA. Previous investigations of opioid receptor binding, carried out in whole-brain homogenates, have, however, failed to detect changes. In the present study, quantitative autoradiography was used to measure μ and κ opioid receptor binding in discrete brain regions of streptozotocin-treated diabetic rats. Measurement was limited to regions that previously displayed opioid binding changes in chronically food-restricted rats, since our primary aim is to identify brain mechanisms that mediate adaptive responses to persistent metabolic need and adipose depletion. Diabetics displayed strong trends or statistically significant changes which matched seven of the thirteen binding changes observed in food-restricted rats. In no case did diabetics display changes in the opposite direction. The two statistically significant changes common to food-restricted and diabetic rats are increased κ binding in the medial preoptic area and decreased μ binding in the lateral habenula. The possible functional significance of these changes is discussed.     

Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 163–167, August, 2000     

Effects of central opiate and serotoninergic structures on heart rhythm during acute myocardial ischemia

Electrostimulation of the central gray matter in the sylvian aqueduct and nucleus raphe magnus produced an antiarrhythmic effect during acute myocardial ischemia. Stimulation and blockade of opiate receptors in the central amygdaloid nucleus and lateral hypothalamus with dalargin and naloxone induced the same effect. Destruction of the central gray matter in the sylvian aqueduct and nucleus raphe magnus decreased electrical stability of ischemic myocardium.     

Effect of GABA-ergic agents on the analgesic effect of morphine in rats

In order to detect possible interaction between GABA and opiates, the effects of GABA-ergic drugs on analgesia induced by morphine were studied. The vocalization response to electrical stimulation of the tail in rats was used as an index of the action of morphine. Thiosemicarbazide, an inhibitor of glutamate decarboxylase, and bicuculline, which blocks GABA-ergic receptors, drugs which, it is suggested, can be considered as a group of GABA-negative compounds, weaken and shorten the effect of morphine. Depakine, an inhibitor of -ketoglutarate-GABA-transaminase, like GABA itself, given in large doses (GABA-positive effects) strengthens morphine analgesia and prolongs its effect. The possible causes of these relations between GABA and opiates are discussed.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 35–37, July, 1979.