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

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae. 329 87

The purpose of the present study was to make a functional dissection of the respiratory action of opioids, by their restricted application to the ventral surface of the medulla oblongata and to the rostro-dorsal surface of the pons in cats. The effects were compared to those induced after intracerebroventricular (i.c.v.) injection. Two mu-agonists, morphine and D-Ala2-Me-Phe4-Met(O)ol5-enkephalin (FK-33824), and the delta-agonist D-Ala2-D-Leu5-enkephalin (DADLE) were used. When applied to the ventral medullary surface, the opioids selectively depressed the generating mechanisms for tidal volume and the response to CO2, whereas the frequency was increased. The application to the rostral dorsal surface of the pons was followed by a selective depression of the respiratory frequency. By intracerebroventricular administration, the opioids depressed both the tidal volume and frequency generating mechanisms. The effects were always reversed by naloxone. The pontine structures were more sensitive to the action of the opioids than were the medullary centres. These findings suggest that the opioids can interact with different populations of respiratory neurones and that the respiratory output differs depending on the group of neurones selectively affected and the function they subserve in regulating respiratory activity.
 ...
PMID:Differential respiratory patterns induced by opioids applied to the ventral medullary and dorsal pontine surfaces of cats. 392 84

1 Excitatory junction potentials (e.j.ps) were recorded with intracellular microelectrodes from smooth muscle cells of the mouse isolated vas deferens. The amplitude of the e.j.p. was used as a measure of transmitter release evoked by applying single pulse stimuli to the intramural nerves. 2 Cyclic adenosine 3',5'-monophosphate (cyclic AMP) and dibutyryl cyclic AMP (db cyclic AMP, up to 1 mM) depressed the amplitude of e.j.ps, probably by interacting with extracellular sites on the nerve terminals, similar to those responsive to adenosine. 3 The phosphodiesterase inhibitors, 1-methyl-3-isobutyl xanthine (IBMX) and 1-ethyl-4-hydrazino-1H-pyrazolo(3,4-b)pyridine-5-carboxylic acid, ethylester, hydrochloride (SQ20,006) increased e.j.p. amplitude; this increase was much greater when the phosphodiesterase inhibitor was applied together with db cyclic AMP. 4 Neither the cyclic nucleotides nor the phosphodiesterase inhibitors altered the resting membrane potential of smooth muscle cells. 5 The amplitude of the e.j.p. was depressed by normorphine, D-Ala2-Met5-enkephalinamide (DAEA) and D-Ala2-D-Leu5-enkephalin (DADL) with respective EC50s of 560 nM, 49 nM and 510 pM. 6 There was no change in the EC50 for normorphine in the presence of cyclic AMP (1 mM) or in the presence of a combination of IBMX (50 microM) and db cyclic AMP (500 microM). Similarly, the depression of the e.j.p. by DAEA or DADL was not affected by the combination IBMX (500 microM) and db cyclic AMP (250 microM). 7 These findings provide evidence against the hypothesis that a reduction in cyclic AMP levels in nerve terminals is an essential step in the inhibition by opiates and opioid peptides of transmitter release.
 ...
PMID:A study of the role of cyclic adenosine 3',5'-monophosphate in the depression by opiates and opioid peptides of excitatory junction potentials in the mouse vas deferens. 625 91

Using a simple method to measure respiratory rate, it was clearly shown that the depression of respiratory rate caused by morphine, ethylketazocine or [D-Ala2,D-Leu5]enkephalin was not altered by the highly selective, irreversible mu-antagonists, beta-funaltrexamine (beta-FNA) at a dose which produced marked antagonism of morphine antinociception. These results indicated that antinociception and depression of respiratory rate are mediated by different receptor interactions. However using a different method to measure respiratory rate (body plythesmograph), beta-FNA caused substantial antagonism of morphine-induced respiratory depression indicating that the degree to which mu-receptor interactions contribute to the depression of respiratory rate depends on the methodology. Possible explanations for this difference are discussed. It is concluded that careful consideration of the methodology must be given when one measures respiratory rate and caution must be exercised if measurement of rate alone is used to assess opioid-induced respiratory depression.
 ...
PMID:Determination of the relative involvement of mu-opioid receptors in opioid-induced depression of respiratory rate by use of beta-funaltrexamine. 630 47

The effects of [Leu5]enkephalin and morphine were studied in the cat superior cervical ganglion (SCG) in situ and in vitro. [Leu5]enkephalin induced dose-dependent ganglionic hyperpolarization. Morphine was 50 times less potent than [Leu5]enkephalin in inducing ganglionic hyperpolarization. The effect of [Leu5]enkephalin was antagonized by naloxone in 7 times higher than equimolar doses. It is suggested that the hyperpolarizing effect of [Leu5]enkephalin in the cat SCG could be mediated mainly by delta-opiate receptors. [Leu5]enkephalin in doses inducing dose-dependent hyperpolarization depressed ganglionic transmission by at most 25%. Morphine was 130 times less potent in inducing depression of ganglionic transmission than ganglionic hyperpolarization. [Leu5]enkephalin in the range of doses inducing dose-dependent ganglionic hyperpolarization depressed dose-dependently the stimulus-bound decremental oscillatory potentials evoked by the muscarinic drug McN-A-343. The results indicate that the muscarinic type of ganglionic activity seems to be a more important target for the proposed inhibitory modulatory action of [Leu5]enkephalin than does the nicotinic type of synaptic transmission in the cat SCG.
 ...
PMID:The actions of [Leu5]enkephalin and morphine in cat sympathetic ganglion. 630 55

To further investigate the role of opioid peptides and specific opiate receptor subtypes in central cardiovascular regulation by hindbrain nuclei, mu (D-Ala2,MePhe4,Gly-ol5 enkephalin, DAGO), delta (D-Ala2,D-Leu5 enkephalin, DADL) or kappa (MRZ 2549) agonists were microinjected into hindbrain nuclei of spontaneously or artificially respired, pentobarbital-anesthetized rats. In the nucleus tractus solitarius (NTS), DAGO and DADL (0.3 nmol) elicited pressor responses and tachycardia. MRZ (3.0-16 nmol) depressed blood pressure in spontaneously breathing rats, but accelerated heart rate in artificially ventilated animals. Blood pressure and heart rate of spontaneously breathing animals were not altered following nucleus ambiguus (NA) injection of DAGO or DADL (0.3 nmol), but were elevated in artificially respired animals; MRZ (3.0-10 nmol) injected into the NA depressed blood pressure in both groups. These data suggest that in the absence of respiratory depression, NTS and NA mu receptors mediate pressor responses and tachycardia; kappa receptors in the NA mediate a decrease in blood pressure but cardioacceleration in the NTS.
 ...
PMID:Differential cardiovascular effects mediated by mu and kappa opiate receptors in hindbrain nuclei. 631 99

In an effort to identify delta-receptor-specific properties for opioid modulation of seizure activity, studies were conducted with ICI 154,129, a putative delta-receptor antagonist, in the rat flurothyl test. Rats were pretreated i.c.v. with ICI 154,129 (50 micrograms) which, at this dose, does not alter normal seizure thresholds. Mean seizure thresholds for control groups (i.c.v. saline) ranged between 323-349 sec. In this test, D-Ala2-D-Leu5 enkephalin (20 micrograms, i.c.v.), metkephamid (40 mg/kg, s.c.), and etorphine (20 micrograms/kg, s.c.) raised seizure thresholds by 117, 128, and 140% of control, respectively. Meperidine (25 mg/kg, s.c.) lowered seizure thresholds by 14% less than control. Pretreatment with ICI 154,129 failed to antagonize the proconvulsant action of meperidine or the anticonvulsant and behavioral depressant actions of etorphine. The increases in seizure threshold produced by DADL and metkephamid (two delta-directed ligands) were significantly attenuated by ICI 154,129. However, the DADL-induced wet-shakes, rigid immobility, and behavioral depression were insensitive to ICI 154,129. These data indicate that ICI 154,129 possesses delta-receptor antagonistic properties in this in vivo model of seizure activity. Furthermore, since only the changes in seizure threshold were antagonized, it may be inferred that opioid-induced behavioral depression and DADLE wet-shakes are not a function of delta-receptor activity.
 ...
PMID:A selective role for delta-receptors in the regulation of opioid-induced changes in seizure threshold. 631 16

The respiratory and cardiovascular effects of the highly selective mu opioid agonist, D-Ala2, MePhe4, Gly- ol5 enkephalin ( DAGO ) and the relatively selective delta agonist, D-Leu5 enkephalin (DADL) were compared following injection (0.1 microliter) into the nucleus ambiguus (NA) of spontaneously-breathing and artificially-respired, pentobarbital-anesthetized rats. In non-ventilated animals, the opioids elicited dose-related (3 X 10(-11) -3 X 10(-9) M), naloxone-reversible depression of respiratory rate (RR) without altering the tidal volume. Mean arterial pressure (MAP) was unchanged at small doses and decreased at the largest dose; heart rate (HR) was unchanged. In artificially-respired animals, both peptides elicited dose-related, naloxone-reversible increases in mean arterial pressure and heart rate; DAGO was significantly more potent than DADL (P less than 0.01). Given the relative potency and selectivity of the opioids tested, these findings are consistent with the conclusion that mu receptors may selectively mediate the respiratory and cardiovascular actions of opioids in an important brain stem cardiorespiratory center in the rat. Moreover, these data indicate the importance of respiratory effects on the cardiovascular activity of centrally administered opioids.
 ...
PMID:Selective cardiorespiratory effects mediated by mu opioid receptors in the nucleus ambiguus. 632 52

The respiratory action of morphine, D-Ala2-D-Leu5-enkephalin, and D-Ala2-Me-Phe4-Met(O)ol5-enkephalin, restrictively applied to the dorso-rostral surface of the pons, was studied in anesthetized cats. Frequency was selectively and dose-dependently depressed, down to apnea, whereas tidal volume and its response to CO2 either remained unchanged or were increased. Similar effects were observed in vagotomized and decerebrate cats. From these and previous (1) results, it can be concluded that the medullary and pontine structures related to respiration are differentially affected by opioids. Pontine nuclei are more sensitive to opioid depression and account for changes in frequency, whereas medullary depression results in reduction of tidal volume and CO2 sensitivity.
 ...
PMID:Participation of pontine structures in the respiratory action of opioids. 636 54

Dermorphin, an opioid peptide occurring in amphibian skin, exerted a depressive effect on locomotor activity of C57B1/6 mice and an analgesic effect when injected intravenously. Intracerebroventricular injections of dermorphin enhanced locomotor activity and resulted in analgesia. A stimulating effect of intracerebroventricular administration on locomotor activity was also induced by shorter homologues of dermorphin and [D-Ala2, Leu5]enkephalinamide, while beta-endorphin produced a depression. It is suggested that dermorphin acts on central receptor populations activated by morphine and enkephalins.
 ...
PMID:Behavioural data on dermorphins in mice. 712 88


<< Previous 1 2 3 Next >>