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R G Dyer

Publications and source records attributed to R G Dyer.

At least 37 records · Page 2Linked to original sources
PubMed1988

Hypothalamic opioid mechanisms controlling oxytocin neurones during parturition.

The influences of opioids on oxytocin secretion and parturition were investigated in the rat. Morphine, administered centrally or peripherally, severely delays the course of established parturition. This delay is accompanied by reduced plasma oxytocin levels and is overcome by treatment either with the opioid antagonist naloxone, or by infusion of oxytocin. An endogenous opioid regulatory mechanism inhibiting oxytocin secretion becomes activated immediately prior to and during parturition. This mechanism does not operate earlier in pregnancy or during normal lactation and is not seen in nonpregnant animals. Naloxone acutely speeds up the course of established parturition, an effect accompanied by greatly elevated plasma oxytocin levels. The mechanisms underlying opioid regulation of oxytocin neurones were investigated at two sites. Precipitated withdrawal from chronic morphine treatment causes hypersecretion of oxytocin. This response is mediated by greatly enhanced electrical activity in the perikarya of oxytocin neurones indicating the presence of opioid receptors on oxytocin neurones and/or on their afferent input. Opioid receptors are also present in the neurohypophysis where they exert direct and noradrenaline mediated effects on secretion from oxytocin terminals in vitro.

Animals↗
PubMed1988

Opioid modulation of the response of preoptic neurones to stimulation of the ventral noradrenergic tract in female rats.

1. Experiments were undertaken on twenty-nine ovariectomized female rats, pretreated with oestrogen and anaesthetized with urethane, to test the hypothesis that opioid peptides regulate noradrenergic transmission in the medial preoptic area and thereby influence the neural circuitry controlling the secretion of luteinizing hormone. 2. Extracellular recordings were obtained with glass micropipettes from ninety-four neurones in the medial preoptic area. These recordings were continued whilst both the ventral noradrenergic tract, the noradrenergic projection to the medial preoptic area, and orthodromic pathways originating in the arcuate nucleus, the main source for endogenous opioid peptides in the hypothalamus, were stimulated electrically. Forty of the ninety-four neurones responded to stimulation at one or both of the test sites. 3. Electrical stimulation of the ventral noradrenergic tract excited fifteen neurones (greater than 30% change in number of action potentials recorded during the 'response time period') and inhibited a further ten cells. When the nucleus arcuatus was stimulated electrically thirteen cells were inhibited and twelve neurones showed an excitatory response. 4. The opioid antagonist naloxone (80 mM) and/or morphine (50 mM) were ejected into the immediate vicinity of eighty-six of the recorded cells by passage of balanced currents (range 15-80 nA) through a multi-barrelled electrode glued to the recording electrode. The tip of the drug-containing electrode was about 15-25 microns behind the tip of the recording electrode. 5. The ionophoretic application of naloxone, during electrical stimulation of the ventral noradrenergic tract, diminished the inhibitory response in four of ten cells and enhanced the excitatory response in nine out of fifteen neurones. By contrast, morphine diminished the excitatory response in seven of these fifteen cells tested, an effect that was prevented by the simultaneous application of naloxone. 6. Similarly, the application of naloxone during stimulation of the nucleus arcuatus reduced the inhibitory effect in eight out of thirteen cells. When four of these eight responsive neurones were exposed to morphine either the effect of naloxone was reversed or, when given alone, the inhibition was enhanced. 7. Finally, for seventeen cells categorized as non-responsive to stimulation at either site, the application of naloxone during hind brain stimulation revealed an excitatory input from the ventral noradrenergic tract in seven cases. 8 The experiments demonstrate that opioid peptides modulate the neural inputs to the medial preoptic area arising from the nucleus arcuatus and the ventral noradrenergic tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

Endogenous opioid actions and effects of environmental disturbance on parturition and oxytocin secretion in rats.

Blood samples were taken from conscious, chronically-catheterized rats during parturition for measurement of oxytocin by specific radioimmunoassay. After the birth of the 3rd pup, rats were allowed to remain in their nesting cage (undisturbed rats) or were transferred for 45 min to a glass bowl (disturbed rats); at the time of transfer, rats were given an i.v. injection of the opioid antagonist naloxone or saline vehicle. Subsequent parturition was prolonged in saline-treated disturbed rats, but not in naloxone-treated disturbed rats. Parturition was significantly hastened in naloxone-treated undisturbed rats. Naloxone injections were followed by a large rise in plasma oxytocin concentrations in disturbed and undisturbed rats. We conclude, from a statistical analysis of the relationship within experimental groups between plasma oxytocin concentration and speed of parturition, that the effects of disturbance and of naloxone upon parturition may be accounted for, at least in part, by their effects upon oxytocin release. However, the effects of disturbance on parturition may not be mediated entirely by activation of opioid pathways. Naloxone did not potentiate oxytocin release in non-pregnant rats, or on Day 1 post partum, but did potentiate oxytocin release on Day 22 of pregnancy even in rats before the onset of parturition. Endogenous opioid pathways regulating oxytocin release therefore appear to be active during late pregnancy and during parturition itself.

Animals↗
PubMed1987

Effect of neonatal testosterone upon opioid receptors and the content of beta-endorphin, neuropeptide Y and neurotensin in the medial preoptic and the mediobasal hypothalamic areas of the rat brain.

The content of beta-endorphin, neuropeptide Y and neurotensin-like immunoreactivity (beta-End, NPY and NT), and the total number of opioid binding sites, were measured in the medial preoptic area (MPOA) and mediobasal hypothalamus (MBH) of ovariectomized adult rats which were oestrogen-primed. The rats had been injected neonatally with either testosterone propionate (TP) or vehicle (oil). NPY content was found to be higher in the MPOA of animals which received TP, whereas no significant difference was observed in the MBH NPY content. However, the NT concentration in the MBH of TP-treated rats was almost twice the amount detected in oil-treated rats and with this peptide no significant changes were detected in the MPOA. Finally, beta-End and the total number of opioid binding sites were reduced in both the MPOA and MBH of the rats which were exposed to TP neonatally. Since exposure to testosterone neonatally masculinises the rat hypothalamus, to the extent that female rats cannot generate oestrogen-stimulated prolactin and luteinizing hormone surges, we suggest that the neurochemical changes reported in this paper reflect some aspects of this sexual differentiation of the rat hypothalamus.

Animals↗
PubMed1987

Neonatal testosterone modifies LH secretion in the adult female rat by altering the opioid-noradrenergic interaction in the medial preoptic area.

Noradrenergic-opioid interaction in the medial preoptic area (MPOA) was examined in ovariectomised adult rats which were oestrogen-treated and had been injected neonatally with either testosterone propionate (TP) or vehicle (oil). The first experiment involved electrical stimulation of the ventral noradrenergic tract (VNAT) in anaesthetised rats. Blood samples were collected before and after the stimulation to determine plasma levels of luteinising hormone (LH). Approximately half of the animals received naloxone i.v. 15 min before the onset of stimulation. In all groups, stimulation of VNAT elicited a significant increase in plasma LH concentration. However, pretreatment with naloxone in androgenised rats, but not in oil-treated animals, almost doubled the LH increment due to stimulation. Naloxone had no effect on plasma LH concentrations in unstimulated control rats. In the second experiment hypothalamic slices containing the MPOA were preincubated with [3H]noradrenaline [( 3H]NA) and then subjected to electrical field stimulation under the conditions of (a) no drug added and (b, c) morphine superfusion without and with naloxone. The opioid agonist morphine significantly reduced the net release of [3H]NA in normal and TP-treated female rats. Addition of equimolar naloxone reversed this effect in normal females, whereas in the androgenised group it not only reversed this effect but elicited a significant increase in [3H]NA release. From these data we conclude that (1) neonatal testosterone treatment alters noradrenergic-opioid interaction regulating LH secretion in adult females and (2) the site of this change may be the presynaptic opioid input to the noradrenergic terminals in the MPOA.

Animals↗
PubMed1987

Opioid peptides inhibit the release of noradrenaline from slices of rat medial preoptic area.

Previous circumstantial evidence suggested that endogenous opioid peptides inhibit an excitatory noradrenergic projection to the medial preoptic area (MPOA), and thereby suppress the activity of neurones containing luteinising hormone-releasing hormone and thus systemic concentrations of luteinising hormone (LH) itself. In this paper, we report that electrically stimulated release of 3H-Noradrenaline (3H-NA) from perifused slices of rat MPOA is diminished when opioid agonists are added to the incubation medium. Thus, morphine (10 microM), beta-Endorphin (1 microM) and met-Enkephalin (1 microM), but not Dynorphin A (1-8) (1 microM), caused a significant decrease in electrically stimulated 3H-NA release. The inhibition was reversed by addition of naloxone (10 microM) to the perifusion medium but 3H-NA release was unaffected by dopamine or acetylcholine (or their antagonists sulpiride and atropine, respectively), or serotonin, neurotensin, muscimol or bicuculline (the latter two being agonist and antagonist respectively for the GABA A receptor). Therefore, the experiments provide direct evidence that brain opioids modulate the noradrenergic input to MPOA neurones and support the hypothesis that this may be one mechanism for the regulation of LH secretion.

Animals↗
PubMed1987

Stress-induced disruption of parturition in the rat may be mediated by endogenous opioids.

Plasma samples were obtained before and during parturition from conscious rats implanted chronically with a jugular cannula. Rats were either allowed to remain in their nesting cage throughout parturition, or were moved immediately following the birth of the second or third pup into an empty glass chamber. The time-course of parturition was prolonged for mother rats which were moved in mid-parturition to this unfamiliar environment. However, in rats given an i.v. injection of the opioid antagonist naloxone at the time of transfer, parturition followed a normal time-course, and plasma oxytocin levels were significantly higher than in animals injected with saline. Thus our hypothesis is that stress activates opioid pathways which delay parturition by inhibiting oxytocin release. Opioid-mediated mechanisms may similarly be responsible for some problems in human parturition.

Animals↗
PubMed1986

Morphine inhibits electrically stimulated noradrenaline release from slices of rat medial preoptic area.

Experiments were undertaken to investigate whether the release of noradrenaline (NA) in the preoptic area of female rats is modulated by opiate mechanisms. Slices (300 microns) of preoptic area were incubated individually after loading with 3H-NA and then subjected to electric field stimulation. Morphine (10 microM) significantly reduced the amount of NA released in response to electrical stimulation, an effect that was completely prevented by simultaneous exposure to equimolar naloxone. This inhibitory action of morphine was not dependent upon prior exposure to oestrogen.

Animals↗
PubMed1986

Neonatal testosterone potentiates stimulated prolactin secretion in adult oestrogen-primed rats.

Blood samples were collected from oestrogen-primed gonadectomized adult rats before and after electrical stimulation of the preoptic part of the hypothalamus. Six groups of rats were used for the experiments. These were (a) males castrated on the first day of life, (b) males castrated after puberty, (c) females ovariectomized after puberty and (d), (e) and (f) females given testosterone propionate at birth (1.25, 0.125 and 0.0125 mg/rat respectively). Neonatal exposure of the female rats to testosterone caused a dose-dependent increase in the amounts of prolactin released to levels significantly (P less than 0.01) higher than those observed in male animals and in untreated females. The results indicate that although neonatal testosterone inhibits oestrogen-stimulated prolactin secretion in adult rats, the neuroendocrine apparatus controlling secretion of the hormone is capable of being activated to greater effect after exposure to androgens at the time of birth.

Animals↗
PubMed1985

Electrical stimulation of the ventral noradrenergic tract (VNAT) releases hypothalamic noradrenaline and stimulates prolactin secretion in ovariectomized female rats treated with oestrogen.

Electrical stimulation of the ventral noradrenergic tract (VNAT) caused a significant fall in the hypothalamic content of noradrenaline in ovariectomized female rats which had been treated with oestrogen. No similar effect was observed in the cerebral cortex, which implies that the stimulation did not affect the dorsal noradrenergic tract. In parallel experiments with groups of similarly treated rats, VNAT stimulation was found to increase release of prolactin from the pituitary gland, and this increase was significantly enhanced in animals which had been stressed by fasting for 3 days.

Animals↗
PubMed1985

Fasting impairs LH secretion in female rats by activating an inhibitory opioid pathway.

Two experiments were undertaken to investigate the way that fasting impairs LH secretion and to assess whether endogenous opioid mechanisms might be responsible for the impairment. In the first experiment, pulsatile LH secretion was measured in a total of 51 chronically ovariectomized female rats. Initially 29 rats were subjected to food withdrawal for 24, 48, 72 or 120 h before the experiment. When compared with data collected from eight unfasted control rats, the 120-h fast was found to reduce significantly the mean peak and trough values of the LH pulses measured. However, in a subsequent study, the inhibition of pulsatile LH secretion by a 120-h fast was prevented in a group of eight rats given the opioid antagonist naloxone hydrochloride before the start of the blood-sampling period. Naloxone was without effect on pulsatile LH secretion in eight unfasted control rats. In the second experiment, plasma LH concentrations were measured before and after unilateral electrical stimulation of the ventral noradrenergic tract (VNAT) in ovariectomized female rats pretreated with oestradiol benzoate. In 17 rats VNAT stimulation caused a significant rise in plasma LH, but after a 72-h fast this rise was significantly less than in unfasted control rats. However, pretreatment of fasted rats with naloxone (n = 9) significantly enhanced the VNAT-stimulated release of LH to the control values. Naloxone did not potentiate VNAT-stimulated LH release in unfasted animals (n = 6) or LH release in control unstimulated rats (n = 12). The experiments indicate that both pulsatile LH secretion, and LH release caused by VNAT stimulation, are impaired by an acute fast.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1985

Central opioids: a possible role in parturition?

Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.

Animals↗
PubMed1984

Relative effectiveness of naloxone and MR2266 in potentiating oestrogen-stimulated luteinizing hormone surges in ovariectomized female rats.

The oestrogen-stimulated surge of luteinizing hormone (LH) can be inhibited by opiates and potentiated when endogenous opiate pathways are blocked by naloxone. Experiments were undertaken to allow an assessment to be made of the opiate receptor category predominantly responsible for inhibiting LH secretion. Thus the effects of MR2266 (primarily a mu and kappa antagonist) and naloxone (primarily a mu and delta antagonist) on LH surges were compared. At a dose of 4.5 mg/kg, administered three times in the 6 h preceding the LH surge, naloxone significantly potentiated LH release whereas this dose of MR2266 was without effect. However at the lower dose of 0.5 mg/kg, administered three times also, the size of the LH surge was significantly increased by MR2266 but not by naloxone.

Animals↗
PubMed1984

Reproducible increases in intramammary pressure after spinal cord stimulation in lactating rats.

Intramammary pressure was recorded in anaesthetized lactating rats during electrical stimulation of the anterolateral pathways in the T12/L1 region of the spinal cord. In 18 rats, electrical stimulation at 10 Hz or more for 10-30 s caused a reproducible increase in intramammary pressure. The mammary gland responses were similar to those resulting from stimulation of the neurohypophysis with the same parameters, and were eliminated after complete destruction of the neural stalk; they were not associated with any consistent change in blood pressure. In 3 rats, a mammary gland response to spinal cord stimulation was obtained only after administration of the beta-adrenergic blocker, propranolol, which facilitates suckling-induced reflex milk-ejections. These results suggest that spinal cord stimulation can cause the release of oxytocin; the functional significance of such a release is discussed in relation to the milk-ejection reflex.

Animals↗
PubMed1984

Anaesthesia with alphaxalone plus alphadolone acetate blocks the oestrogen-stimulated LH surge and impairs pulsatile LH secretion in ovariectomized female rats.

Two experiments were undertaken to assess further the action of the steroid anaesthetic alphaxalone upon LH secretion in chronically ovariectomized female rats. For the first experiment, 31 rats were given two injections of oestradiol benzoate (20 micrograms/100 g body weight), each 72 h apart, to stimulate an LH surge 6 h after the second injection. However, one group of seven rats was anaesthetized with alphaxalone throughout the 6-h period and a second group of eight was similarly anaesthetized only for the last 2 h of the 6-h period. The steroid-stimulated LH surge was blocked in both groups of rats anaesthetized with alphaxalone. The second experiment involved a comparison of pulsatile LH secretion in animals which were either unanaesthetized (n = 8) or anaesthetized with alpha xalone (n = 9). In six out of nine rats the anaesthetic did not affect the maximum or minimum plasma LH concentrations but significantly slowed the frequency at which LH pulses were measured. In the remaining three anaesthetized rats the drug blocked pulsatile LH secretion. The experiments confirm that some secretion of LH continues during alphaxalone anaesthesia but indicate also that the drug has a more deleterious action upon the oestrogen-stimulated LH surge than believed hitherto.

Anesthetics↗