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J E Olley

Publications and source records attributed to J E Olley.

At least 19 recordsLinked to original sources
PubMed1992

Sub-chronic exposure to opiates in the rat: effects on brain levels of substance P and calcitonin gene-related peptide during dependence and withdrawal.

Substance P (SP) and calcitonin gene-related peptide (CGRP) are putative transmitters in the central and peripheral (sensory) nervous systems. In this study, we examined the effects of dependence on and withdrawal from morphine and methadone on brain SP and CGRP content. Female Long Evans rats (70-100 g) were provided with plain drinking water or solutions containing opiate. No choice of drinking fluid was allowed. The maintenance level of each opiate (0.8 and 0.4 mg/ml for morphine and methadone, respectively) was continued for 4 days. Following an injection with naloxone (10 mg/kg i.p.) or saline, animals were decapitated 0, 20, or 60 min later and regional brain peptide content was measured by specific radioimmunoassays. SP and CGRP content in opiate-maintained and naive animals were similar following saline injection. However, following naloxone injection in morphine-maintained animals, SP content was elevated in the hypothalamus and midbrain at 20 min, but by 60 min was no longer distinguishable from basal (0 min) level. CGRP content was increased in the medulla oblongata and followed a comparable time course but, unlike SP, was not altered in the hypothalamus or midbrain. No alterations were observed in methadone-maintained animals. These results correlated with the peak of the behavioral morphine withdrawal syndrome and were consistent with the comparatively milder abstinence encountered in methadone medication.

Animals↗
PubMed1992

Morphine and methadone dependence in the rat: withdrawal and brain met-enkephalin levels.

Opioids were administered to female Long Evans rats in their drinking water. Maintenance doses of 0.8 and 0.4 mg/ml for morphine and methadone, respectively, were achieved using an ascending dosage schedule. Rats were decapitated 0, 20, or 60 min after naloxone (10 mg/kg, IP) or saline. Brain met-enkephalin-like immunoreactivity (ME-LI) was determined by radioimmunoassay (RIA). In morphine-drinking animals, ME-LI in all regions of the brain was unaltered following saline administration; however, 20 min after naloxone injection ME-LI had increased in the striatum, hypothalamus, midbrain, and pituitary. By 60 min, ME-LI was no longer elevated. In both methadone- and water-drinking rats, ME-LI did not deviate from normal. These elevated levels of ME-LI, 20 min after naloxone-precipitated withdrawal in morphine-dependent rats, coincided with the peak of behavioural signs in the precipitated withdrawal syndrome. The milder behavioural disturbances observed in the withdrawal of methadone-drinking rats were consistent with the unaltered ME-LI in these animals.

Animals↗
PubMed1990

A sensitive and specific enzyme-linked immunosorbent assay for methionine enkephalin sulphoxide.

An enzyme-linked immunosorbent assay (ELISA) for the sulphoxide derivative of the opioid peptide methionine enkephalin (MOE) was developed and found to be sensitive and highly specific. Methionine enkephalin itself showed only low cross-reactivity (1.8%) in the assay while leucine enkephalin and the endorphins showed cross-reactivity no higher than 0.6%. Given the ease of application, low cost and stable nature of the label, this technique is a useful alternative to existing radioimmunoassays for the peptide.

Animals↗
PubMed1990

Enzyme immunoassay for methionine-enkephalin sulfoxide.

1. An immunoassay technique employing an enzyme-labelled ligand was developed for the sulfoxide derivative of the opioid peptide methionine-enkephalin (MOE). 2. The sensitivity of the enzyme immunoassay (EIA) was approximately twofold higher than that achieved in the radio-immunoassay (RIA) using tritiated ligand. Cross-reactivities of leucine-enkephalin and beta-endorphin with the EIA were less than 0.1%, while that with Gly-Gly-Phe-Met and oxidized Gly-Gly-Phe-Met were 2.5% and 10.2%, respectively. 3. These results indicate that the EIA is a useful alternative to the RIA for the assay of small peptides.

Cross Reactions↗
PubMed1990

Effects of morphine, H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and B-HT920 on non-cholinergic nerve-mediated bronchoconstriction in pithed guinea-pigs.

1. Electrical stimulation (1 ms, 5 Hz, 80 V) for 5 or 15 s at the level of C4-T1 in the spinal canal of artificially respired pithed guinea-pigs (which had received intravenously (i.v.) (+)-tubocurarine chloride 2 mg kg-1, atropine sulphate 2 mg kg-1 and pentolinium tartrate 5 mg kg-1) caused constriction of airways, indicated by increased insufflation pressure. 2. This non-cholinergic constriction was inhibited by morphine (1-3 mg kg-1, i.v.), the peripherally acting mu-receptor agonist, H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA, 0.1-1 mg kg-1, i.v.) or the alpha 2-adrenoceptor agonist B-HT920 (1-3 mg kg-1, i.v.). 3. The effects of either morphine (3 mg kg-1, i.v.) or DALDA (1 mg kg-1, i.v.) were inhibited by naloxone (3 mg kg-1, i.v.). Idazoxan (3 mg kg-1, i.v.) inhibited the anti-constrictor effect of B-HT920 (3 mg kg-1, i.v.), but not that of DALDA (0.1 mg kg-1, i.v.). 4. Thus activation of peripheral mu-opioid receptors or alpha 2-adrenoceptors inhibits airways constriction induced by non-cholinergic nerve stimulation in the pithed guinea-pig. This preparation therefore provides a further method for the in vivo examination of the effects of drugs on non-cholinergic tracheobronchial constrictor nerve function.

Adrenergic alpha-Agonists↗
PubMed1989

Use of methionine-enkephalin sulfoxide and leucine-enkephalin radio-immunoassays for the measurement of enkephalins in the rat brain.

1. A radio-immunoassay (RIA) for methionine-enkephalin sulfoxide was developed and was used to measure methionine-enkephalin, after oxidation, in the rat brain. 2. The RIA was performed together with assays that use commercially available met- and leu-enkephalin antisera. 3. Evidence is presented here indicating that antisera raised against the native met-enkephalin peptide underestimate met-enkephalin content due to loss of immunoreactivity after oxidation of peptide. 4. These results show that a more accurate measurement of met-enkephalin may be obtained by using the met-enkephalin sulfoxide RIA. The cross-reactivity of met-enkephalin with the leu-enkephalin RIA was diminished following oxidation of peptide.

Animals↗
PubMed1989

Effects of subacute opioid administration during late pregnancy in the rat on the initiation, duration and outcome of parturition and maternal levels of oxytocin and arginine vasopressin.

1. The effects, on parturition in the rat, of subacute and acute opioid administration were studied. Further experiments investigated the role of modulation of maternal plasma and pituitary oxytocin (OXY) and arginine vasopressin (AVP) levels in these effects. 2. Subacute opioid (M320, buprenorphine or bremazocine) administration prolonged the gestation of rats. This was accompanied by toxic effects on the offspring. Acute subcutaneous (s.c.) M320 (10 micrograms/kg) administration was accompanied by prolonged gestation without toxic effects. 3. Subacute M320 (10 micrograms/kg, s.c., twice daily) treatment was accompanied by increased interbirth intervals in parturient rats. 4. Maternal OXY but not AVP release, as assessed by measurement of plasma and pituitary immunoreactivity, was elevated during and up to 1 h after the completion of parturition. Subacute M320 treatment did not inhibit this elevated OXY release.

Animals↗
PubMed1989

mu- and K-opiate receptor agonists reduce plasma neurohypophysial hormone concentrations in water-deprived and normally hydrated rats.

1. The effects of mu- and K-opiate receptor agonists on plasma concentrations of immunoreactive (ir) oxytocin (OXY) and arginine vasopressin (AVP) in normally hydrated and water-deprived rats were studied. 2. Water-deprivation for 36 h elevated both plasma ir-OXY and ir-AVP concentrations of Long-Evans rats. These elevated levels were lowered in a dose-dependent manner after subcutaneous administration of bremazocine (3-10 micrograms/kg), M320 (10-100 micrograms/kg) or morphine (0.1-10 mg/kg). Comparable reductions of plasma concentrations of ir-AVP and ir-OXY were observed. 3. Plasma concentrations of ir-OXY and ir-AVP of normally hydrated Long-Evans rats were lower after subcutaneous administration of bremazocine (10 micrograms/kg), M320 (10 micrograms/kg) and morphine (1.0 mg/kg). 4. These data suggest that both mu- and K-opiate receptor agonists inhibit both OXY and AVP release from the neurohypophysis of rats.

Animals↗
PubMed1989

Opiate receptors: ligands and methods of study.

1. An introduction to the current knowledge of the mu-, kappa- and delta-opioid receptors will be given. 2. The many problems associated with opiate ligands with respect to selectivity, potency, slow receptor kinetics, instability and poor access to the central nervous system will be discussed. 3. Current systems for analysis of the receptor profile of opiate ligand activity will be given. 4. The properties of opioid ligands will be discussed in the context of the identified problems.

Animals↗
PubMed1988

Comparison of the oxytocin response to water-deprivation, hyperosmolarity and administration of morphine or naltrexone in lactating and virgin female rats.

In rats, lactation is accompanied by changes in the pattern of oxytocin (OXY) release associated with the onset of reflex milk ejection during suckling. The present study attempted to identify further differences between OXY release in virgin and lactating rats. Basal levels of plasma immunoreactive (ir)-OXY and the OXY responses to both water-deprivation and intraperitoneal administration of hypertonic saline were lower in lactating than in virgin female rats. Subcutaneous administration of morphine (0.01-10.0 mg/kg) was followed by a dose-related reduction in plasma ir-OXY levels in virgin but not lactating rats. The OXY response to naltrexone (3 mg/kg) was similar in both types of animal. Lactation-associated changes in the control of metabolism and/or release of OXY may involve changes in neurohypophysial morphology but do not involve alteration of tonic endogenous opioid influences on OXY release.

Animals↗
PubMed1988

Effects of exposure in utero to methadone and buprenorphine on enkephalin levels in the developing rat brain.

Rat pups were exposed in utero to the opiates methadone or buprenorphine by administering subcutaneous injections to the mothers daily for the duration of pregnancy. Met- and Leu-enkephalin in the brains of the pups were measured by specific radioimmunoassays. Methadone at 8 mg/kg but not 4 mg/kg significantly reduced enkephalin levels in the striatum. Buprenorphine (1 and 2 mg/kg) did not affect peptide levels in any brain region. The results suggest that buprenorphine has minimal effect on the endogenous opioid system compared with methadone. However, the toxicity data indicate that he survival of the newborn is adversely affected by in utero exposure to buprenorphine.

Animals↗
PubMed1988

Enzyme immunoassay of buprenorphine.

Assays for the potent, highly lipophilic analgesic buprenorphine described in the literature include the radioimmunoassay (RIA), radioreceptor assay (RRA) and selected ion-monitoring. Problems arise with the use of hazardous and unstable ligand in the RIA and RRA and the need for an extraction step for RRA and selected ion-monitoring. An enzyme immunoassay (EIA) was developed to allow rapid and simple analysis of plasma concentrations of drug without these disadvantages. The N-dealkylated derivative of buprenorphine, norbuprenorphine, was labelled with beta-D-galactosidase using the linking agent N-(gamma-maleimidobutyryloxy) succinimide. This enzyme-labelled hapten was used to develop an EIA for buprenorphine. The assay is sensitive enough to measure 10 pg of buprenorphine. Endogenous opioid peptides do not cross-react in the assay; norbuprenorphine itself was completely cross-reactive. Since the presence of plasma (100 microliters) has no effect on the standard curve, plasma levels in humans were determined by this EIA without extraction after intravenous or sublingual administration of the drug. The EIA therefore represents a good alternative to existing assays for buprenorphine-like material with the advantages of simplicity, safety, sensitivity and ease of handling.

Adult↗
PubMed1988

Studies of the effects of subacute treatment with N-(cyclopropylmethyl)-19-isopentylnororvinol (M320) on timing of parturition in the rat.

1. Administration of 10 micrograms kg-1 of the long lasting potent kappa- and weaker mu-opioid agonist N-(cyclopropylmethyl)-19-isopentylnororvinol (M320) twice daily from day 20 of gestation prolonged the internal gestation period of the rat and retarded the development of the offspring in the perinatal period. 2. The capacities of myometrial, placental and cervical tissues to produce prostaglandin E2 (PGE2) were not affected by M320 treatment. 3. During the period in which parturition normally occurred in saline-treated rats, foetal pituitary levels of immunoreactive oxytocin (ir-OXY) but not immunoreactive arginine-vasopressin (ir-AVP) were greater in M320-compared to saline-treated animals. Following the completion of parturition, foetal pituitary ir-OXY and ir-AVP levels continued to rise in saline-treated rats, but fell dramatically in rats treated subacutely with M320. 4. These data indicate that subacute treatment with M320 may inhibit foetal oxytocin release at term. This foetal OXY release may be a stimulus for the initiation of labour.

Animals↗
PubMed1986

The effects of N-(cyclopropylmethyl)-19-isopentylnororvinol (M320), a potent agonist at kappa- and mu-opiate receptors, on urine excretion of rats.

The effects of N-(cyclopropylmethyl)-19-isopentylnororvinol hydrochloride (M320) on urine excretion by rats were investigated. Further studies, using rabbit isolated vas deferens, investigated its interactions with kappa-opiate receptors. The output of urine for a 2 h period after M320, administered subcutaneously to normally hydrated Long Evans rats, showed a bell-shaped dose-response relationship, the maximum effect occurring after 10 micrograms kg-1. Urinary retention contributed to but did not fully account for the weaker diuresis after high doses. Attenuation of the ascending portion of the dose-response curve to M320 occurred after 1 and 10 mg kg-1 but not 0.1 mg kg-1 of naltrexone intraperitoneally. M320 in low doses (3-10 micrograms kg-1) caused a small but significant increase in sodium excretion. M320 (30 micrograms kg-1) reduced both sodium and potassium excretion. M320 (10 micrograms kg-1 s.c.) did not increase the volume of urine voided in 2 h by Brattleboro rats showing diabetes insipidus, even when urine excretion was reduced to normal by 1 week of vasopressin replacement. The volume of urine voided in 4 h by Brattleboro rats was progressively reduced to zero by M320 (10-100 micrograms kg-1 s.c.). Urinary retention contributed to but did not account for this reduction. Plasma levels of immunoreactive arginine vasopressin (ir-AVP) were reduced in both normal and dehydrated Long Evans rats after doses greater than 1 microgram kg-1 M320 s.c. In vitro, M320 caused persistent inhibition of twitches of the electrically stimulated rabbit vas deferens (IC50 1.7 nM). 8 These data suggest that M320 has potent opioid agonist activity at K-receptors and at higher concentrations stimulates mu- receptors. In the rat, its activity on K-receptors is associated with diuresis and suppression of plasma vasopressin levels. The antidiuresis seen after high doses may be due to its activity on mu-receptors, possibly at a central site.

Animals↗
PubMed1983

Antinociceptive actions of morphine and buprenorphine given intrathecally in the conscious rat.

1 The antinociceptive effects of morphine and buprenorphine given intrathecally and subcutaneously have been compared in the conscious rat. 2 In the paw pressure test, when given subcutaneously buprenorphine 0.001-0.1 mg/kg s.c., was approximately 100 times more potent than morphine 0.1-3 mg/kg s.c., but in the hot plate test, buprenorphine 0.03-3.0 mg/kg s.c., produced a bell-shaped dose-response curve of low maximum effect and was about equipotent with morphine 0.03-3 mg/kg s.c. 3 When given intrathecally buprenorphine 10 micrograms and morphine, 10-60 micrograms, were approximately equipotent in both paw pressure and hot plate tests. Furthermore, morphine produced these effects at 1/25th of the minimum effective parenteral dose while the dose of buprenorphine exceeded the parenteral dose. 4 It is concluded that the predominant site of the analgesic action of buprenorphine is supraspinal. The significance of these findings in relation to the role of spinal opiate receptors is discussed.

Analgesics↗