Biomedical subjects

R F Parrott

Publications and source records attributed to R F Parrott.

At least 37 records · Page 2Linked to original sources

PubMed1996

Bacterial endotoxin-induced gene expression in the choroid plexus and paraventricular and supraoptic hypothalamic nuclei of the sheep.

The febrile and neuroendocrine responses to circulating endotoxin are effected, at least in part, by a central action of prostaglandins with interleukins serving as intermediaries. Data from rodents suggest that prostaglandin and interleukin (IL-1 beta) synthesis in response to endotoxin challenge may occur within the circumventricular organs of the brain, especially the choroid plexus; the present study investigated this possibility using the sheep as an experimental model. A pyretic dose of bacterial endotoxin (40 micrograms lipopolysaccharide) was given intravenously to sheep (n = 5) and the effect on gene expression in the choroid plexus after a 40 min interval was compared with that observed in vehicle-treated animals (n = 5) using in situ hybridisation histochemistry. Evidence of activational and synthetic events following endotoxin administration was provided by significant increases in c-fos (P < 0.05) and IL-1 beta (P < 0.01) mRNA expression. Constitutive cyclooxygenase (cox-1 mRNA) and inducible cyclooxygenase (cox-2 mRNA) synthesis were unchanged. The investigation also sought to provide evidence for endotoxin effects on neuroendocrine activity in this species by examining changes in hypothalamic gene expression. The results showed that c-fos mRNA increased in the paraventricular (P < 0.01) and supraoptic (P < 0.05) nuclei and that CRH mRNA was upregulated in the paraventricular nucleus (P < 0.001). However, in agreement with previous work, there was no change in vasopressin gene expression although oxytocin mRNA was enhanced throughout the paraventricular nucleus (P < 0.05). These findings suggest the following: (1) possible involvement of the choroid plexus in the response of sheep to immunological challenge: (2) endotoxin-induced changes in gene expression in the ovine hypothalamus similar in those caused by other stressors: and (3) possible changes in oxytocin synthesis concomitant with fever in the sheep.

Animals↗

PubMed1996

Effects of the novel cholecystokinin analogue Suc-Trp-N(Me)-Nle-Asp-Phe-NH2 on feeding and cortisol release in pigs.

Suc-Try-N-(Me)-Nle-Asp-Phe-NH2 is a succinylated tetrapeptide derived from the C-terminal sequence of cholecystokinin octapeptide (CCK-B), which has been shown to have high agonist affinity for CCKB receptors. To test the validity of the hypothesis that implicates central CCKB receptors in the aetiology of stress-related disorders, such as anxiety and panic, we argued that activation of these receptors by a CCKB receptor agonist should (i) suppress feeding motivation in hungry animals and (ii) increase plasma concentrations of the stress hormone cortisol. The effects of systemic and central administration of Suc-Try-N-(Me)-Nle-Asp-Phe-NH2 were, therefore, investigated on operant food intake and cortisol secretion in pigs. Intravenous administration of Suc-Try-N-(Me)-Nle-Asp-Phe-NH2 (0.5-5 micrograms/kg) did not affect operant feeding in food-deprived pigs, although the highest dose (5 micrograms/kg) produced a small but significant (p < 0.05) increase in plasma cortisol levels 5-30 min after injection. Intracerebroventricular injection of Suc-Try-N-(Me)-Nle-Asp- Phe-NH2 (1-5 micrograms) had no effect on operant feeding and cortisol secretion in this species. The results obtained in this study indicate that central CCKB receptors are unlikely to be involved in stress-related behaviours in pigs.

Amino Acid Sequence↗

PubMed1996

Effects of centrally administered prostaglandin EP receptor agonists on febrile and adrenocortical responses in the prepubertal pig.

Febrile and adrenocortical responses to central (lateral ventricle) injections of prostaglandin E2 (PGE2) and E-series prostanoid receptor agonists (EP1, EP2, EP3, subtypes) were investigated in prepubertal pigs. In Experiment 1, administration of PGE2, (1.4, 5.6 nmol) produced dose-related increases in core temperature and plasma cortisol concentrations. In Experiment 2, approximately equimolar (1.2 to 1.4 nmol) amounts of EP1, EP2, and EP2/EP3 agonists were compared. The EP2 and EP2/EP3 prostanoids raised core temperature, whereas the increase induced by the EP1 agonist was not significant. Similarly, although all of the agonists appeared to stimulate cortisol release, these results were also not significant. In Experiment 3, pigs treated with an EP3 agonist (1.3 nmol) showed marked febrile and adrenocortical responses. The results of these experiments are compared with data from the rat using the same agonists and route of administration. The findings are also discussed in relation to the distribution of receptor populations in vascular and synaptosomal compartments of the porcine brain.

Adrenal Cortex↗

PubMed1996

Hormonal and physiological effects of a 15 hour road journey in sheep: comparison with the responses to loading, handling and penning in the absence of transport.

A controlled study was carried out to investigate the physiological effects of road transport on sheep. Animals (n = 10; body weight 38.9 +/- 1.3 kg), previously with catheters in their jugular veins, were rounded up and loaded onto a vehicle where they were held in a communal pen with eight other lambs. Blood samples were taken at 30 min intervals during the next 15 h while the vehicle remained stationary or was driven a distance of 548 miles (876 km). Measurements were made of plasma concentrations of cortisol, prolactin, creatine phosphokinase and lactase dehydrogenase isozymes and also of plasma osmolality, haematocrit and body weight; heart rate was also recorded in one animal. Loading and the start of driving produced large increases in cortisol and prolactin concentrations. Heart rate also increased whereas osmolality and haematocrit decreased. The major changes in hormone release occurred in the first 3 h period while, during the remaining 12 h, the stimulatory effect of transport was present but small. Body weight loss was similar under both stationary and driven conditions.

Animal Welfare↗

PubMed1996

The effects of central administration of the CCK-B receptor agonist pentagastrin on feeding and cortisol release in sheep.

In order to test the validity of the hypothesis that implicates central cholecystokinin-B (CCK-B) receptors in the etiology of anxiety and panic disorders, we argued that activation of these receptors by the CCK-B receptor agonist pentagastrin should (i) suppress feeding in hungry animals, and (ii) increase plasma concentrations of the stress hormone cortisol. We found that intracerebroventricular administration of pentagastrin (4 and 10 micrograms) did not inhibit feeding nor increase cortisol secretion in sheep (n = 6). Moreover, the peptide did not produce behavioral responses in the animals. We conclude that central CCK-B receptors are unlikely to be involved in behaviors associated with anxiety or panic in this species.

Animals↗

PubMed1996

Cyclooxygenase-independent mechanisms are not involved in the antipyretic action of indomethacin in the prepubertal pig.

The effects of an intravenous, antipyretic dose of indomethacin (IND) on basal and prostaglandin E2 (PGE2)-induced changes in body temperature were investigated in an attempt to assess whether noncyclooxygenase pathways contribute to the pharmacological actions of IND in swine. The results showed that IND lowered basal temperature for about 90 min but failed to modify the febrile effects of PGE2. These findings suggest that IND acts only as an antagonist of constitutive and inducible cyclooxygenase in this species. Neuroanatomical and sex-steroid dependent mechanisms are discussed as explanations for the apparently different actions of IND in rodents and ungulates.

Analgesics, Non-Narcotic↗

PubMed1995

Prostaglandin-dependent c-Fos expression in the median preoptic nucleus of pigs subjected to restraint: correlation with hyperthermia.

Restraint using a nose snare activates the hypothalamo-pituitary-adrenocortical axis and induces c-Fos expression in the paraventricular hypothalamus in the pre-pubertal pig; this procedure also induces hyperthermia in pigs. To investigate the neural mechanisms involved in this thermoregulatory response, c-Fos protein was quantified in the forebrains of pigs snared for 15 min (n = 5), injected with saline vehicle via an i.v. catheter (controls, n = 4) or treated with the cyclooxygenase inhibitor, indomethacin (2 mg/kg i.v.), prior to a 15 min period of snaring (n = 3). There were few c-Fos immunopositive nuclei in the median preoptic nucleus of non-stressed animals. By contrast, c-Fos expression in this region was enhanced by snaring (P < 0.001) and this response was markedly reduced (P < 0.002) by indomethacin. The results suggest that restraint induces a prostaglandin-mediated increase in core temperature (stress hyperthermia) in the growing pig that involves the activation of preoptic thermoregulatory neurons.

Animals↗

PubMed1995

Restraint, but not frustration, induces prostaglandin-mediated hyperthermia in pigs.

Three experiments were carried out to investigate stress hyperthermia in prepubertal pigs. Experiment 1 examined the effect of frustrative nonreward (psychological stress) on deep body temperature in animals (n = 7) trained to make operant responses for food following a 17.5-h period of deprivation. There was no change in body temperature when the feeders were switched off whereas there was a small increase (NS) during normal operant feeding that might be attributable to physical exertion. In Experiment 2, the effects of 15-min physical restraint (snaring) were examined in the same group of animals. This procedure induced a significant (p < 0.01) rise in core temperature that was completely abolished by prior administration of a cyclooxygenase inhibitor (indomethacin, 2 mg/kg given intravenously). The final experiment investigated the effects of snaring on plasma cortisol concentrations. Blood samples were taken from indwelling catheters in pigs (n = 5) subjected to 15-min restraint with, or without, indomethacin pretreatment. Snaring produced a significant (p < 0.001) increase in cortisol release that was not affected by the administration of indomethacin. These results suggest that snaring, a physical stress that may also have energy expenditure components, induces a prostaglandin-mediated hyperthermic response in the growing pig.

Animals↗

PubMed1995

Increased body temperature, cortisol secretion, and hypothalamic expression of c-fos, corticotrophin releasing hormone and interleukin-1 beta mRNAs, following central administration of interleukin-1 beta in the sheep.

There is evidence to indicate that cytokines of the interleukin series act within the brain to influence physiological responses to pathological states or stressful events. This investigation examined the effects of intracerebroventricular (lateral ventricle) injection of human recombinant interleukin-1 beta (IL-1 beta) on body temperature, hormone (catecholamine, cortisol, prolactin, growth hormone) release and hypothalamic expression of c-fos, corticotrophin-releasing hormone (CRH), vasopressin (AVP) and IL-1 beta mRNAs in the sheep. A preliminary study showed that central administration of 10 micrograms IL-1 beta significantly (P < 0.05) increased body temperature (by 1.2 degrees C) over a 140 min period but did not affect catecholamine secretion. A second experiment using graded doses (100 ng, 1 microgram, 10 micrograms) of IL-1 beta indicated that only the highest dose significantly (P < 0.01) increased cortisol concentrations and that none of the treatments altered the secretion of prolactin or growth hormone. In a third study, changes in gene expression in the hypothalamus were examined using in situ hybridization histochemistry following treatment with 10 micrograms IL-1 beta. The results showed that IL-1 beta increased c-fos mRNA in the paraventricular (PVN, P < 0.05) and supraoptic (SON, P < 0.05) nuclei, CRH mRNA in the PVN (P < 0.01) and IL-1 beta mRNA in the PVN (P < 0.05). There was, however, no change in AVP mRNA in either the PVN or the SON.

Animals↗

PubMed1995

Hyperthermic and endocrine effects of intravenous prostaglandin administration in the pig.

Experimentally induced fever is accompanied by a variety of hormonal changes, and there is evidence to suggest that some of these responses may be mediated by prostaglandins. However, little is known about the endocrine effects of peripherally administered prostaglandins, especially in domesticated species. In this study, the effects of intravenous prostaglandin E2 (PGE2; 20 micrograms/kg) on deep body temperature and plasma concentrations of cortisol, lysine vasopressin (LVP), and growth hormone were investigated in prepubertal pigs (n = 6) prepared with venous catheters and sampled at 10-min intervals for 3 hr. PGE2-induced hyperthermia, which lasted for the duration of the study, was accompanied by a 70-min increase in cortisol and LVP concentrations. Moreover, this hyperthermic response was checked when LVP levels were high. These results indicate that a fever-inducing intravenous injection of PGE2 produced a marked anterior and posterior pituitary hormone response in growing pigs. Also, the transient increase in LVP may be correlated with a central action of the hormone, limiting the extent of the fever. In addition, because the majority of the animals exhibited mild hyperthermia (0.5 degrees C) under control conditions, the results suggest that, in a given population of pigs, there may be some animals that exhibit stress-induced hyperthermia.

Animals↗

PubMed1995

Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal pig.

Prepubertal pigs (n = 8) treated with bacterial endotoxin (20 micrograms lipopolysaccharide; LPS) exhibited a sustained (4 h) hyperthermia, increased plasma concentrations of cortisol, prolactin, growth hormone and vasopressin, but no change in adrenaline or noradrenaline levels was observed. All these effects were prevented or attenuated when the animals were pretreated intravenously with the cyclo-oxygenase inhibitor indomethacin (IND; 2 mg/kg). Similarly, in pigs (n = 3 per treatment) given IND, LPS or IND + LPS, parallel changes in the neuronal expression of c-Fos were observed in hypothalamic regions concerned with thermoregulation, neurohypophysial secretion, and the control of pituitary-adrenocortical function. The stimulatory action of LPS in the median preoptic, supraoptic and paraventricular nuclei was prevented by IND, whereas IND given alone was without effect. These findings suggest that inducible cyclo-oxygenase pathways are responsible for the febrile and neuroendocrine effects of endotoxin in this species.

Animals↗

PubMed1995

Intravenous administration of cholecystokinin (CCK) stimulates prolactin and growth hormone release in the pig.

Blood samples were taken from prepubertal pigs (n = 7) surgically prepared with venous catheters before, and at intervals during the 30 min period after, administration of physiological saline (vehicle) or sulphated cholecystokinin octapeptide (CCK) (0.3, 0.7 and 1.3 mu g/kg). Plasma concentrations of prolactin and growth hormone were measured by radioimmunoassay. Statistically significant dose-related increases in prolactin occurred mainly in the first 10-min period following CCK administration. The peptide also stimulated growth hormone secretion although in a less consistent manner, with the increases tending to occur over a longer time period. Together with earlier reports showing that CCK induces cortisol release in pigs, these results suggest that the peptide's effect on anterior pituitary function could be indicative of a stress response.

Animals↗

PubMed1994

Hyperthermia-associated changes in Fos protein in the median preoptic and other hypothalamic nuclei of the pig following intravenous administration of prostaglandin E2.

Changes in body temperature and hypothalamic Fos production were investigated in pigs injected intravenously with prostaglandin E2 (PGE2, 20 micrograms/kg). PGE2 produced a sustained (> 150 min) hyperthermia (0.7-1 degree C) and significant increases in Fos labelling in the supraoptic and paraventricular nuclei. In addition, PGE2 induced Fos production in the median preoptic nucleus, a region previously demonstrated to be involved in thermoregulation in this species.

Animals↗

PubMed1994

Differential stressor effects on the concentrations of cortisol, prolactin and catecholamines in the blood of sheep.

Adult wether sheep (n = 8) were subjected to 60 minutes of psychological (isolation) or physical (transport simulation/standing in water) stress, or a control handling procedure in the home pen. Blood samples were taken before and during these treatments and the plasma concentrations of cortisol, prolactin, noradrenaline and adrenaline determined. All the stressors significantly increased plasma cortisol concentrations (P < 0.001) whereas only transport simulation increased prolactin secretion (P < 0.005). Noradrenaline concentrations showed little change in response to the various treatments, with the exception of isolation which produced a small non-significant increase (P < 0.08). All the stress procedures stimulated adrenaline release within the first 10 minutes but the most marked effects were seen after transport simulation and isolation, both of which induced a significant increase throughout the treatment period (P < 0.01).

Animals↗

PubMed1994

Central effects of CCK ligands in pigs making operant responses for food.

The effects, on operant feeding, of intracerebroventricular (ICV) injections of the CCKA receptor agonist A71623, the CCKB receptor agonist A63387, and the CCKA receptor antagonist A70104 were investigated in prepubertal pigs. In overnight starved animals, feeding was inhibited by 20, 5, and 1 micrograms doses of A71623 and by 20, but not 5 or 1 micrograms doses of A63387. In a second experiment, although pigs pretreated centrally with A70104 (20 micrograms) showed a tendency to eat more, the effect was not statistically significant. Furthermore, this dose of A70104 did not prevent the inhibition of feeding induced by a subsequent ICV injection of CCK (1 microgram). These findings support the view that exogenous CCK reduces food intake in pigs by acting, primarily, on CCKA receptors.

Animals↗

PubMed1994

The CCKA receptor antagonist devazepide inhibits the effect of apomorphine on vasopressin release in pigs.

1. A transient increase in plasma vasopressin concentrations represents a physiological correlate of nausea in animals that vomit. 2. The CCKA receptor antagonist devazepide has previously been shown to inhibit vasopressin release induced in pigs by intravenous (i.v.) CCK. 3. This study investigated whether devazepide (70 micrograms/kg i.v.) would affect vasopressin secretion induced in pigs (n = 6) by the emetic drug apomorphine (25 micrograms/kg i.v.). 4. Apomorphine stimulated vasopressin release in the 30 min period following injection; this effect was prevented by prior administration of devazepide. 5. The results suggest that CCKA receptor antagonists may have the ability to prevent nausea and/or emesis.

Animals↗

PubMed1994

Expression of c-fos in the ovine brain following different types of stress, or central administration of corticotrophin-releasing hormone.

Expression of c-fos protein was examined in the brains of sheep (n = 2 per treatment) subjected to physical stress in a transport simulator, the psychological stress of isolation, insulin-induced hypoglycaemia or intracerebroventricular (I.C.V.) injection of ovine corticotrophin-releasing hormone (CRH). As control procedures, two sheep were given I.C.V. injections of saline and one animal received no treatment. Fos expression was induced in the hypothalamic paraventricular nucleus by transport simulation, isolation and hypoglycaemia, and also in the hypothalamic supraoptic nucleus by hypoglycaemia. Labelled nuclei were also seen in the brainstem in the region of the area postrema following transport simulation, isolation and insulin treatments. These results indicate that c-fos expression in the ovine CNS is a useful marker for the identification of brain regions activated by stressors.

Animals↗

PubMed1994

Centrally administered vasopressin modifies stress hormone (cortisol, prolactin) secretion in sheep under basal conditions, during restraint and following intravenous corticotrophin-releasing hormone.

The effects of central (lateral ventricle) injections of vasopressin (2.5, 25 or 250 ng) on cortisol and prolactin release were investigated in castrated male sheep (N = 6) under basal (non-stress) conditions, during 120min of physical restraint and following peripheral injection of ovine corticotrophin-releasing hormone (oCRH). Cortisol and prolactin concentrations in non-stressed sheep were raised significantly (p < 0.05) in the 120 min following administration of 250 ng of vasopressin. The prolactin response to restraint stress was decreased (p < 0.05) in the 30-min period following central injection of 250 ng of vasopressin. The stimulatory effect of oCRH on cortisol release was enhanced (p < 0.05) by vasopressin (25 and 250 ng), whereas prolactin levels decreased (p < 0.02) in the 30-min period following injection of the highest dose of vasopressin. None of the central doses of vasopressin significantly altered plasma levels of this hormone, although vasopressin secretion was increased during restraint.

Animals↗