Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study in unanesthetized goats, we demonstrated that cerebrospinal fluid levels of beta-endorphin were significantly elevated after 2.5 h of inspiratory flow-resistive loading. Naloxone (NLX) (0.1 mg/kg) administration partially and transiently reversed the tidal volume depression seen during loading. In the current study, we tested the hypothesis that endogenous opioid elaboration results in depression of respiratory output to the diaphragm. In six studies of five unanesthetized goats, tidal volume (VT), transdiaphragmatic pressure (Pdi), diaphragmatic electromyogram (EMGdi), and arterial blood gases were monitored. A continuous NLX (0.1 mg/kg) or saline (SAL) infusion was begun 5 min before an inspiratory flow-resistive load of 120 cmH2O.l-1.s was imposed. Our data show that the depression of VT induced by the load was prevented by NLX as early as 15 min and persisted for 2 h. At 2 h, Pdi was still 294 +/- 45% of the base-line value compared with 217 +/- 35% during SAL. There was no difference in EMGdi between the groups at any time. However, the augmentation of Pdi was associated with a greater increase in end-expiratory gastric pressure in the NLX group. We conclude that the reduction in VT and Pdi associated with endogenous opioid elaboration is not mediated by a decrease in neural output to the diaphragm, but it appears to be the result of a decrease in respiratory output to the abdominal muscles.
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PMID:Naloxone alters the early response to an inspiratory flow-resistive load. 253 92

Modulatory influences of the mu opioid agonist morphine and the kappa opioid agonist U-50, 488H on field-evoked potentials from the main olfactory bulb (MOB) in response to stimulation of the olfactory nerve were studied. Topically administered morphine upon the MOB dorsal surface produced a noloxone-sensitive depression of the late component of the response without modifying the early one, while topical administration of U-50, 488H suppressed both the early and the late components. Naloxone did not antagonize U-50, 488 effects. Results indicate that mu and kappa opioid agonists can interfere with sensory transmission at the level of second-order neurons of the olfactory pathway, the mitral and/or tufted cells.
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PMID:Mu and kappa opioid modulation of olfactory bulb evoked potentials. 256 34

1. Repetitive stimulation (10-20 Hz, 0.5-5 s duration) of the preganglionic nerves to ganglia on the surface of the urinary bladder of the cat produced a prolonged inhibition (duration, 30-65 s) of the postganglionic action potentials, elicited by low-frequency stimulation (0.25-1 Hz) of another preganglionic nerve to the same ganglion. 2. Intra-arterial administration of naloxone, an opiate antagonist (20-50 micrograms/kg), reduced the magnitude and duration of this heterosynaptic inhibition and also blocked the depression of ganglionic transmission elicited by the intra-arterial administration of leucine-enkephalin (0.1-10 micrograms/kg). 3. Naloxone did not alter adrenergic inhibition elicited by repetitive stimulation of the hypogastric nerve or exogenous noradrenaline. Naloxone did not alter the postganglionic firing elicited by single stimuli or trains of low-frequency (1-3 Hz) stimuli to the preganglionic nerves. 4. Heterosynaptic inhibition was not altered by the administration of antagonists for alpha-adrenergic (dihydroergotamine, prazosin, yohimbine), muscarinic (atropine), purinergic (theophylline) or GABAergic (picrotoxin) receptors. 5. A delta-selective opiate receptor agonist, DSLET (D-Ser2-leucine-enkephalin-Thr), inhibited parasympathetic ganglionic transmission in low doses (mean threshold dose, 0.02 microgram/kg, I.A.), whereas a mu-opiate receptor agonist, morphine sulphate, produced only a small depression in larger doses (mean threshold dose, 100 micrograms/kg, I.A.). Ethylketocyclazocine, which has an affinity for kappa-receptors did not alter transmission in relatively large doses (1 mg/kg, I.A.). 6. These findings coupled with previous immunocytochemical demonstrations of leucine-enkephalin-like immunoreactivity in preganglionic nerve terminals in bladder ganglia suggest that opioid peptides released endogenously from preganglionic nerves are involved in delta-receptor-mediated inhibitory mechanisms at cholinergic synapses in bladder ganglia.
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PMID:Enkephalinergic inhibition in parasympathetic ganglia of the urinary bladder of the cat. 260 Aug 44

Acute opioid physical dependence refers to the withdrawal symptoms precipitated by an opioid antagonist administered after a single dose or short-term infusion of an opioid agonist. This phenomenon is particularly interesting given that the abstinence syndrome has generally been thought to develop only after chronic exposure to opioid agonists. The purpose of this study was to determine the minimum time after agonist administration when antagonist-precipitated withdrawal could be observed. Naloxone (10 mg/70 kg) was administered i.m. either 0, 15, 45 or 90 min after single i.m. injections of morphine (18 mg/70 kg) in five nondependent male opiate users. Physiological and subjective report measures revealed no effect of morphine or naloxone at the 0 and 15 min morphine-naloxone interval conditions; however, before the naloxone challenge 45 and 90 min post-morphine, agonist effects (e.g., miosis, respiratory depression and good drug effect subjective ratings) were clearly evident. Naloxone reversed these effects to premorphine levels and simultaneously precipitated subjective symptoms and observer rated signs of opiate withdrawal. Thus, this study showed that antagonist-precipitated withdrawal in humans was first observed 45 min after agonist administration. Further, the onset of naloxone-precipitated withdrawal effects closely paralleled the onset of morphine agonist effects. The results of this study suggest that adaptational changes underlying the development of physical dependence begin within minutes after acute exposure to an opiate.
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PMID:Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval. I. 276 Aug 39

The effects of bombesin and related peptides on functionally identified single dorsal horn neurones were studied using iontophoresis and extracellular recording in the anaesthetized and spinalized cat. Bombesin selectively depressed superficial dorsal horn neurones (in laminae I-III). The depression was of spontaneous activity as well as of synaptically elicited responses to natural stimulation of the cutaneous receptive field. Bombesin preferentially depressed neurones that responded to noxious stimulation of the cutaneous receptive field. Naloxone, bicuculline and caffeine failed to block the depression by bombesin, suggesting that the effect of the peptide may be direct and not through the indirect activation of an inhibitory system mediated by opioids, by gamma-aminobutyric acid (GABA) or by purines, respectively. Iontophoretic application of neuromedin B (n = 3) and neuromedin C (GRP-10) (n = 7) induced a similar depression to that observed with bombesin. These results provide physiological evidence that a bombesin-like peptide may play a role in the mediation or the modulation of sensory transmission in the superficial dorsal horn of the spinal cord.
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PMID:Bombesin, neuromedin B and neuromedin C selectively depress superficial dorsal horn neurones in the cat spinal cord. 279 Apr 61

1 The effects of opioids on synaptic transmission in cat sacral parasympathetic colonic ganglia were studied in vitro, using intracellular electrophysiological techniques. Electrical stimulation of the pelvic nerve evoked fast excitatory postsynaptic potentials (e.p.s.ps), which were blocked by hexamethonium and tetrodotoxin. 2 [D-Pen2, D-Pen5] enkephalin and [Met5]enkephalinamide, delta-opioid receptor agonists, caused concentration-dependent, reversible depression of fast e.p.s.ps, but had no effect on depolarizations evoked by pressure ejection of the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium. Cell transmembrane potential and membrane input resistance were also unaffected. 3 U-50,488H, a kappa-opioid receptor agonist, had a very small depressant action while [D-Ala2, MePhe4, Gly-ol5] enkephalin, a mu-opioid receptor agonist, had no effect on fast e.p.s.p. amplitude. Neither compound affected cell transmembrane potential or membrane input resistance. 4 The inhibitory actions of [D-Pen2, D-Pen5] enkephalin were antagonized by both naloxone, an antagonist at each of the three opioid receptor types, and by ICI 174,864, an antagonist selective for delta-opioid receptors. 5 Naloxone and ICI 174,864 both also potentiated fast e.p.s.p. amplitude per se in 50% of cells tested. 6 It is concluded that exogenous opioids act at presynaptic delta-opioid receptors to inhibit sacral parasympathetic synaptic transmission in cat colonic ganglia in vitro. Furthermore, the effects of opioid antagonists alone, suggest that endogenous opioids may also be released by preganglionic nerve stimulation and so regulate the release of acetylcholine in these ganglia.
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PMID:Delta-opioid receptors mediate inhibition of fast excitatory postsynaptic potentials in cat parasympathetic colonic ganglia. 282 50

Flupirtine, a novel analgesic agent, was tested on nociceptive activity in neurones of the dorsomedial part of the ventral nucleus of the thalamus (VDM) and ascending axons of the spinal cord of rats under urethane anaesthesia. Activity was elicited by supramaximal stimulation of the sural nerve. Flupirtine injected i.v. dose dependently reduced nociceptive activity in the thalamus and ascending axons. The ED50 of flupirtine in depressing the thalamic response was 1.9 mg/kg, and the ED50 in depressing the C fibre-evoked response in ascending axons was 18 mg/kg. Naloxone reduced the depression of the nociceptive response evoked in the thalamus when applied before but not when applied after flupirtine. The results indicate that flupirtine produces analgesia by spinal inhibition of nociceptive impulse transmission from afferent nerve fibres to neurones sending their axons to the brain and, in addition, by supraspinal inhibition of nociceptive impulse transmission to the thalamus. Opioid mechanisms could be involved in these effects.
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PMID:Flupirtine depresses nociceptive activity evoked in rat thalamus. 284 54

Dynorphin A (DYN A) injected intrathecally in the rat produced a significant elevation of the nociceptive threshold, measured by the tail flick test. The highest dose of DYN A (25 nmol) produced maximal elevation of tail flick latency to radiant heat together with hindlimb paralysis and tail flaccidity lasting several hours, thus confirming several previous reports. A lower dose of DYN A (12.5 nmol) produced only a smaller, not constant, short-lasting change in the nociceptive threshold. The vocalization test (electrical stimulation of the tail) gave a different result: the time course curve showed that the antinociceptive effect had worn off 60 min after DYN A 25 nmol. Thus it can be assumed that the prolonged depression of the tail flick reflex was related to motor dysfunction and did not completely reflect the animal's response to painful stimuli. Tolerance to the antinociceptive and motor effects developed after the chronic intrathecal infusion of DYN A with osmotic minipumps. Intrathecal MR 1452 (30 nmol), a purported kappa-receptor blocker, fully prevented the effects of DYN A but not morphine-induced antinociception. Naloxone antagonized DYN A only at a 4 fold higher dose. MR 1452 (90 nmol) administered after DYN A reversed the elevation of the vocalization threshold while tail flick latency remained unmodified. Analysis by high performance liquid chromatography of intrathecally injected radiolabelled DYN A revealed that DYN A was largely broken down about 10 min after its administration. Our results seem to indicate that DYN A in the spinal cord causes alterations in nociception and motor function, clearly distinguishable in time and both mediated by an opioid receptor, probably of the kappa type. However, different mechanism(s), possibly non-opioid in nature, may contribute to the prolonged depression of the tail flick.
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PMID:Characterization of dynorphin A-induced antinociception at spinal level. 286 Oct 98

The high-affinity mu-1 opioid binding site has been implicated in some opioid responses (e.g., supraspinal analgesia) but not others (e.g., respiratory depression) by comparing the actions of naloxone, a short-acting, non-selective antagonist, and naloxonazine, an irreversible and selective mu-1 antagonist. The mu-1 site has been implicated in the opioid component modulating free feeding and deprivation-induced feeding, but not glucoprivic feeding. The present study compared naloxone and naloxonazine antagonism of hyperphagia induced by morphine, ethylketocyclazocine (EKC), dynorphin and d-ala2,d-leu5-enkephalin (DADL) in rats. Morphine produced a dose-dependent (0.01-5 mg/kg) hyperphagia in mildly food-deprived rats that was blocked by naloxone (0.01-10 mg/kg). Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right. These effects could not be fully accounted for by the intrinsic hypophagic properties of these antagonists. EKC produced a dose-dependent (0.5-5 mg/kg) hyperphagia which was blocked by naloxone (10 mg/kg) only at low effective EKC doses. Naloxonazine (10 mg/kg) failed to affect EKC hyperphagia. Naloxone, but not naloxonazine also blocked dynorphin and DADL hyperphagia. These results indicate that feeding induced by opiate and opioid agonists are differentially mediated by the mu-1 and other opioid binding sites; these data contrast with the modulation by the mu-1 site of the supraspinal analgesia induced by each of these agonists.
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PMID:Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. 289 39

Antagonist-precipitated withdrawal after acute opioid administration (acute physical dependence) is an interesting phenomenon in that the opioid abstinence syndrome is generally thought to develop only after prolonged exposure to opioid agonists. The purpose of this study was to examine further this phenomenon in humans by characterizing the antagonist dose-response function. The effects of i.m. naloxone (0, 0.1, 0.3, 1, 3, 10 and 30 mg/70 kg) were assessed 6 hr after single i.m. injections of morphine (18 or 30 mg/70 kg) in six subjects with a history of chronic opiate use. Naloxone reversed residual morphine effects, including miosis and respiratory depression. The degree of reversal was dose-related to 10 mg/70 kg of naloxone with no further increases at the highest naloxone dose. Simultaneously, observer ratings of withdrawal signs and subjective reports of withdrawal symptoms were increased in an orderly dose-related manner to 30 mg/70 kg of naloxone. Reversal of residual morphine effects and onset of precipitated withdrawal were evident by 5-min postnaloxone; peak effects occurred within 15 min. This study confirmed the occurrence of antagonist-precipitated withdrawal after brief opioid exposure in humans, demonstrated the rapid onset of withdrawal effects and characterized the naloxone dose-response function.
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PMID:Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure. 291 67


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