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)

A number of lines of evidence have suggested that alterations in gonadal steroids may modulate opioid function. We report here the effects of manipulation of female gonadal steroids on the opioid feeding system. Naloxone produced a depression of feeding in all groups. Although the group X dosage interaction was not significant, an internally consistent tendency effect of naloxone among the different treatment groups was observed. Estradiol treated rats were 20 times less sensitive to naloxone's suppressive effects of feeding than ovariectomized animals. Sham operated controls and animals treated with estradiol and progesterone had sensitivities to naloxone which were intermediate to those seen in estradiol treated and ovariectomized animals. A significant drug X dosage interaction was present for the ketocyclazocine effects at 4 hours. Overall, ovariectomized animals were resistant to feeding induced by ketocyclazocine compared to the other groups. Ovariectomy significantly decreased ir-dynorphin levels in the cortex and these values were restored towards normal by a combination of estrogen and progesterone treatment. These studies add to the growing literature suggesting a role for the peripheral endocrine system in the modulation of opioid feeding system.
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PMID:The effect of ovariectomy, estradiol and progesterone on opioid modulation of feeding. 615 May 5

Previous studies from our laboratory have shown that the opioid peptide dynorphin-(1-13), although not analgesic when given by itself, can inhibit morphine-induced analgesia in naive mice and potentiate it in morphine tolerant mice. In the present study, we examined the effect of dynorphin-(1-13) with two other dynorphin-like peptides, alpha-neoendorphin and dynorphin-(1-10) amide, on respiration. Our results show that none of the peptides studied had any significant activity on the respiratory rate in mice when given alone. However, in the presence of morphine, dynorphin-(1-13) antagonized the morphine-induced respiratory rate depression in morphine-tolerant animals; alpha-neoendorphin enhanced the morphine-induced respiratory rate depression in naive but had no effect in morphine-tolerant animals and dynorphin-(1-10) amide had no modulatory effect on the morphine-induced respiratory rate depression in either group of animals.
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PMID:Effect of dynorphin-(1-13) and related peptides on respiratory rate and morphine-induced respiratory rate depression. 666 92

The effects of L-Dopa + benserazide (L-Dopa + B) treatment on pre- and postsynaptic dopamine (DA) receptors were studied. Mice treated once daily P.O. with L-Dopa (200 mg/kg) + B (50 mg/kg) or vehicle for 10 days were used on the 11th day. After premedication with reserpine and alpha-methyltyrosine (alpha-MT), apomorphine (0.5-2.0 mg/kg) produced locomotor stimulation which was of equal intensity in the 3 treatment groups, even when the treatment dose of L-Dopa was increased to 400 mg/kg per day. In contrast, low doses of apomorphine (0.1-0.5 mg/kg) produced locomotor depression in B- and vehicle-treated mice but not in L-Dopa + B-treated mice. In rats treated I.P. twice daily with L-Dopa (200 mg/kg) + B (50 mg/kg), B (50 mg/kg) or vehicle for 12 days, apomorphine produced an equivalent degree of stereotypy on the 13th day in each of the 3 treatment groups. There were no treatment group differences in the binding of [3H]-spiperone or [3H]-leu-enkephalin to rat striatal membranes. The data suggest that long-term L-Dopa + B treatment of mice and rats does not change the sensitivity of postsynaptic DA receptors but may affect the sensitivity of DA autoreceptors.
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PMID:Chronic L-dopa treatment of rats and mice does not change the sensitivity of post-synaptic dopamine receptors. 668 48

This study examined the effects of selective activation of kappa 1-opioid receptors on excitatory transmission in substantia gelatinosa (SG) using intracellular recordings from SG neurons in transverse slices of the young rat lumbar spinal cord. Monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) were evoked by orthodromic electrical stimulation of A delta or C primary afferent fibers in the dorsal root after blocking inhibitory inputs with bicuculline and strychnine, NMDA receptors with D-2-amino-5-phosphonovaleric acid and mu- and delta-opioid receptors with CTAP and ICI 174,864, respectively. Bath application of dynorphin A1-17 or U-69, 593 caused dual modulation of the peak amplitude of presumed monosynaptic AMPA receptor-mediated EPSPs, decreasing synaptic potentials at nanomolar concentrations in a majority of SG cells examined (dynorphin, 63%; U-69,593, 91%), and increasing EPSPs at micromolar concentrations. Only the inhibitory action of dynorphin A1-17 was consistently and completely blocked by norbinaltorphimine (nor-BNI). Since U-69,593 and nor-BNI are selective for the kappa 1-opioid receptors, the depression of EPSPs is likely to be mediated by the kappa1-opioid receptors. Under conditions of blockade of synaptic transmission with TTX and mu-and delta-opioid receptors, dynorphin A1-17 and U-69,593 hyperpolarize most of SG neurons and decrease their membrane input resistance, the finding suggesting that direct interaction of kappa-agonists with a postsynaptic receptor is likely explanation for the inhibition of EPSPs. However, in some SG cells, the inhibition of EPSPs appears to be of presynaptic origin since dynorphin A1-17 and U-69,593 did depress the EPSPs in the absence of changes in passive membrane properties. Rp-cAMPS, a membrane permeant potent competitive inhibitor of cAMP-activated protein kinase, prevented the depressant effect of dynorphin A 1-17. This finding suggested a possibility that dynorphin A1-17, acting through a decrease in intracellular cyclic AMP levels, can reduce the synaptic responses of SG neurons. These results provide the first electrophysiological demonstration that the activation of kappa 1-opioid receptors inhibits AMPA receptor-mediated primary afferent neurotransmission in the substantia gelatinosa of the young rat spinal cord. This effect may mediate the ability of kappa-receptor agonists to produce antinociception.
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PMID:kappa-opioid receptor agonists modulate excitatory transmission in substantia gelatinosa neurons of the rat spinal cord. 747 39

In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat, the effects of dynorphin A1-17, U-50,488H and U-69,593 on inward currents induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) were studied under whole-cell voltage-clamp conditions. When the cells were clamped to a holding potential of -60 mV, co-application of dynorphin A1-17 (10(-6) M) and AMPA (2 x 10(-5) M) reversibly decreased the peak amplitude of the initial transient component of the AMPA-induced current in 72% of the examined cells. In addition, dynorphin (10 microM) in perforated patch-recordings consistently produced a decrease in the steady-state component of the AMPA response. The depressant effect was concentration-dependent (IC50 = 86 nM) and reversible. The dynorphin A1-17-induced depression of the AMPA response was associated with slowing of the response kinetics, including both a 10-90% rise-time and time constant of decay. The AMPA-induced currents were modulated by dynorphin not only during the co-administration but also after the removal of the peptide. Dynorphin increased the initial peak AMPA current in 42% of the examined cells. Similar as with dynorphin A1-17, the peak amplitude of the AMPA-induced current was reversibly suppressed in the presence of 1 microM U-50,488H and U-69,593 in 75% and 86% of the examined cells, respectively. Naloxone and the kappa 1-selective antagonist norbinaltorphimine (nor-BNI) blocked the initial depressant but not late excitatory effects of dynorphin A1-17 and U-50,488H. This antagonistic effect of naloxone and norbinaltorphimine suggests that the depressant effect of dynorphin A1-17 on the AMPA-activated conductance is a true opioid, probably kappa 1-opioid receptor-mediated event. In contrast, the dynorphin-induced late potentiation of AMPA/KA responses appears to be a non-opioid effect since it was not inhibited by nor-BNI, CTAP and naltrindole, the selective kappa-, mu- and delta-opioid receptor blocking agents, respectively. Pretreatment of DH neurons with pertussis toxin blocked the depressant action of dynorphin A1-17, indicating that a Gi- or Go-type G protein was required for this effect on AMPA-activated currents. Intracellular dialysis with a highly specific peptide inhibitor (peptide 6-22) of the cAMP-activated protein kinase (PKA), and with Rp-cAMPS, prevented the depressant effect of dynorphin A1-17. In addition, staurosporine, a nonselective kinase inhibitor, blocked the dynorphin depression of the AMPA response.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The opioid peptide dynorphin modulates AMPA and kainate responses in acutely isolated neurons from the dorsal horn. 753 29

The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 1.2 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 1.2 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1.2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration increased and haematocrit decreased during halothane anaesthesia. The concentrations of met-enkephalin, dynorphin and catecholamines did not change and those of beta-endorphin, adrenocorticotrophin, arginine vasopressin and cortisol increased during halothane anaesthesia. Halothane appeared to be a major stimulus to pituitary adrenocortical activation because the adrenocortical secretion was proportional to the amount of halothane inhaled. Beta-endorphin increased proportionally more than adrenocorticotrophin and their plasma concentrations were not correlated, suggesting that they have independent secretion mechanisms.
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PMID:Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia. 770 57

Although plasma levels of Met-enkephalin and beta-endorphin are elevated in patients suffering from liver failure, it is not known whether central nervous system (CNS) opioidergic neurotransmission is altered in these patients. Such changes may contribute to the motor dysfunction, psychiatric abnormalities and CNS depression observed in hepatic encephalopathy (HE). Therefore, Met- and Leu-enkephalin, dynorphin A and beta-endorphin levels were measured in discrete brain regions and plasma from thioacetamide-treated rats in Stages II to IV of HE. Pituitary and plasma beta-endorphin, Met- and Leu-enkephalin concentrations increased with the severity of HE by 50 to 290%. Pituitary and brainstem dynorphin A levels increased whereas plasma levels decreased in rats with thioacetamide-induced fulminant hepatic failure. Both striatal Met- and Leu-enkephalin levels increased and hypothalamic concentrations decreased in HE. Concurrent with the increase in striatal Met-enkephalin levels was a 26 to 48% decrease in the density of striatal and hypothalamic delta receptors. No change in either the density or affinity of radioligand binding to mu or delta receptors was observed in the CNS. Finally, administering (+/-)-naloxone (5 and 10 mg/kg) or (+/-)-naltrexone (5-15 mg/kg), but not (+)-naloxone (10 mg/kg), significantly increased the motor activity of rats with Stage III HE. Whereas elevated plasma levels of opioid peptides may play a role in the peripheral manifestations of hepatic failure (ascites and hypotension), increased CNS levels of these peptides may be involved in the neuropsychiatric abnormalities characteristic of HE. Thus, opioid antagonists may be effective in ameliorating some of the neurological manifestations of HE.
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PMID:Brain and plasma levels of opioid peptides are altered in rats with thioacetamide-induced fulminant hepatic failure: implications for the treatment of hepatic encephalopathy with opioid antagonists. 771 65

The granule cell population response to perforant path stimulation decreased significantly within seconds following release of endogenous dynorphin from dentate granule cells. The depression was blocked by the opioid receptor antagonists naloxone and norbinaltorphimine, suggesting that the effect was mediated by dynorphin activation of kappa 1 type opioid receptors. Pharmacological application of dynorphin B in the molecular layer was effective at reducing excitatory synaptic transmission from the perforant path, but application in the hilus had no significant effect. These results suggest that endogenous dynorphin peptides may be released from a local source within the dentate molecular layer. By light microscopy, dynorphin-like immunoreactivity (dynorphin-LI) was primarily found in granule cell axons in the hilus and stratum lucidum with only a few scattered fibers evident in the molecular layer. At the extreme ventral pole of the hippocampus, a diffuse band of varicose processes was also seen in the molecular layer, but this band was not present in more dorsal sections similar to those used for the electrophysiological studies. Electron microscopic analysis of the molecular layer midway along the septotemporal axis revealed that dynorphin-LI was present in dense-core vesicles in both spiny dendrites and unmyelinated axons with the majority (74%) of the dynorphin-LI-containing dense-core vesicles found in dendrites. Neuronal processes containing dynorphin-LI were observed throughout the molecular layer. The results suggest that dynorphin release from granule cell processes in the molecular layer regulates excitatory inputs entering the hippocampus from cerebral cortex, thus potentially counteracting such excitation-induced phenomena as epileptogenesis or long-term potentiation.
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PMID:Dynorphin opioids present in dentate granule cells may function as retrograde inhibitory neurotransmitters. 791 18

Dynorphin A (1-17) was applied directly onto the spinal cord of rats during electrophysiologic recording of the dorsal root potential (DRP) and the ventral root potentials (VRPs), i.e., monosynaptic reflex and polysynaptic reflexes. Dynorphin application resulted in a dose-dependent depression of the DRP (ED50, 4.5 nmol) which persisted for 30 to 50 min. This effect was not antagonized by nor-binaltorphimine, a kappa-opioid receptor antagonist. During this depression we observed a potentiation of the VRPs which persisted for 4 to 5 min and preceded depression of the VRPs (ED50, 4.0-4.9 nmol). The depression of the VRPs was antagonized competitively by nor-binaltorphimine, although the potentiation was not. beta-Funaltrexamine, a mu-opioid receptor antagonist, had no influence on dynorphin-induced changes of evoked potentials. These data indicate that dynorphin-induced depression of the VRPs is mediated by kappa-opioid receptor activity, whereas neither potentiation of the VRPs nor depression of the DRP appears to be mediated by an opioid receptor effect.
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PMID:Pharmacological characterization of dynorphin A (1-17)-induced effects on spinal cord-evoked potentials. 791 12

Pharmacokinetics and some pharmacological effects of anaesthesia induced by a combination of detomidine, ketamine and guaiphenesin were investigated in eight ponies. Cardiopulmonary function was studied and plasma met-enkephalin, dynorphin, beta-endorphin, arginine vasopressin, adrenocorticotrophin, cortisol, 11-deoxycortisol and catecholamine concentrations were measured. The combination produced slight cardiorespiratory depression, hyperglycaemia and a reduction in haematocrit. There were no changes in plasma opioids, pituitary peptides or catecholamines. Plasma cortisol concentration decreased and plasma 11-deoxycortisol increased indicating a suppression of steroidogenesis. Steady state ketamine and guaiphenesin concentrations were attained during the infusion period, and ketamine concentrations likely to provide adequate analgesia for surgical operations were achieved (more than 2.2 micrograms ml-1). Steady state detomidine concentration was not attained. The ponies took on average 68 minutes to recover to standing and the recovery was uneventful.
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PMID:Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: pharmacokinetics, cardiopulmonary and endocrine effects. 852 79


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