Biomedical subjects

M Hirst

Publications and source records attributed to M Hirst.

At least 55 records · Page 3Linked to original sources

PubMed1987

Slugs and snails and opiate tales: opioids and feeding behavior in invertebrates.

There is accumulating evidence that opioid systems are involved in the regulation of fundamental behavioral and physiological processes in invertebrates. Feeding is a basic physiological function that is essential for maintaining homeostasis. Results of studies examining the feeding responses of molluscs and arthropods treated with various opiate agonists and antagonists indicate that delta, kappa, mu, and possibly sigma opioid systems differentially and selectively mediate the components of their natural feeding behavior. Moreover, it appears that at an early evolutionary stage the mu and kappa systems have developed to selectively affect the components of feeding behavior associated with the acquisition and ingestion of food. In addition, evidence suggests that neuropeptides that have been proposed as possible endogenous antagonists of opioid-mediated feeding in mammals may also be involved in the control of feeding in invertebrates. This indicates that there may be an interplay of opioid agonists and antagonists in the regulation of feeding and satiation in invertebrates analogous to that proposed for vertebrates. Moreover, these findings indicate that opioid influences on feeding have been conserved through evolution.

Animals↗

PubMed1987

Salsolinol in urine following chocolate consumption by social drinkers.

Several studies have shown that there are differential levels of salsolinol excretion between consumers of varying levels of alcohol. The excreted salsolinol may arise during metabolism of alcohol, reflect endogenous biosynthesis of the compound, or result from ingestion of exogenous salsolinol. A previous study identified that salsolinol excretion in urine distinguished light and heavy social drinkers, who had consumed chocolate (containing salsolinol) in combination with a test dose of alcohol. The present study was designed to examine the relationship between social drinking level and the excretion of salsolinol after ingesting dietary salsolinol alone. Participants were 120 volunteers, balanced for gender, social drinking level (abstainers, light, moderate and heavy), and dose of salsolinol. Urine samples were taken on entry, and at 90 minutes and 3 hours after consumption of chocolate. Analysis revealed a dose effect on salsolinol excretion. There were no main or interactive effects of gender or social drinking on salsolinol excretion. The results indicate that the appearance of salsolinol in urine following dietary consumption alone is insufficient to distinguish alcohol consumption levels in social drinkers.

Adult↗

PubMed1986

Prolyl-leucyl-glycinamide (PLG): inhibition of offensive aggression in mice.

The effects on offensive aggression of the endogenous peptide-leucyl-glycinamide (PLG, MIF-1) and the exogenous opiate antagonist, naloxone, were examined in male mice. PLG (0.01-10 mg/Kg) reduced, in a dose-dependent manner, the incidence and intensity of offensive aggression in dominant resident mice. PLG was more potent than naloxone (1.0 mg/Kg). In a number of cases, PLG completely eliminated the display of offensive aggression towards intruder mice. These results raise the possibility that PLG may function as an "anti-aggressive" peptide whose actions may include antagonistic and/or modulatory influences on both opioid and non-opioid systems.

Aggression↗

PubMed1986

An octadecaneuropeptide (ODN) derived from diazepam binding inhibitor increases aggressive interactions in mice.

The effects of intracerebroventricular administrations of an octadecaneuropeptide (ODN) derived from the polypeptide, diazepam binding inhibitor (DBI), on offensive and defensive aggression were examined in male mice. During the initial period after administration (1-5 min) ODN inhibited social and agonistic behavior. At 30 min after treatment, ODN increased, in a dose-dependent manner, the incidence of and intensity of offensive aggression in dominant resident mice. ODN also increased the number of bites required to obtain defeat in subordinate mice during aggressive interactions, as well as reducing subsequent defeat-induced analgesia. These changes in offensive and defensive aggressive behavior that were induced by ODN were reduced by the benzodiazepine receptor antagonist Ro 15-1788. These results suggest that ODN has significant modulatory effects on aggression.

Aggression↗

PubMed1986

Inhibitory influences of FMRFamide and PLG on stress-induced opioid analgesia and activity.

The effects of i.c.v. administration of the peptide FMRFamide (Phe-Met-Arg-Phe-NH2), as well as i.p. injections of PLG (Pro-Leu-Gly-NH2) and the opiate antagonist, naloxone, on immobilization-induced analgesia and locomotor activity were examined in CF-1 and C57BL strains of mice. Both naloxone (1.0 mg/kg) and FMRFamide (0.10-1.0 microgram) blocked the experimentally induced analgesia and activity, whereas PLG (0.10-10 mg/kg) suppressed only analgesia. These results indicate that FMRFamide (or FMRFamide-like neuropeptides) and PLG may function as differential antagonists of the behavioral and physiological consequences of endogenous opioid activation.

Animals↗

PubMed1986

Naloxone-reversible stress-induced feeding and analgesia in the slug Limax maximus.

Exposure to tail-pinch stress increased the thermal nociceptive thresholds and food intakes of the slug, Limax maximus. These stress-induced "analgesic" and feeding responses, which were similar to the behaviors observed after treatment with exogenous opiates, were blocked by the opiate antagonist, naloxone. These results indicate that exposure to stress increases endogenous opioid activity in slugs and induces various behavioral and physiological responses in a manner analogous to that reported in mammals.

Animals↗

PubMed1986

Cleavage of the rat intestinal 1,25-dihydroxyvitamin D3 receptor by an endogenous protease to a form with defective DNA binding.

In this report we describe a form of the 1,25(OH)2D3 receptor which no longer binds to DNA. The defective form of the receptor was produced by the action of an endogenous protease. Rat intestinal receptors, obtained by a two-step procedure of a low salt homogenization followed by extraction of the chromatin pellet with high salt, fail to bind to DNA-cellulose. Inclusion of various serine protease inhibitors during the preparation protects against the loss of DNA binding. Sedimentation analysis in sucrose gradients indicates that the defective receptor is measurably smaller than the native receptor and is unable to aggregate normally under low salt conditions. The size difference, as determined by gel chromatography, is approximately 9,000 Da (56,000 for the protected receptor, 47,000 for the cleaved form). The elution from DEAE-cellulose indicates that the overall charge of both intact and cleaved receptor forms is very similar. Cell fractionation and mixing experiments suggest the enzyme may be located in the lysosomal compartment, organelles which are susceptible to breakage during the extraction procedure. The results demonstrate that an endogenous enzyme preferentially cleaves the 1,25(OH)2D3 DNA binding site resulting in a receptor with altered characteristics. Such an enzymatic activity has not been previously described for the 1,25(OH)2D3 receptor from other tissues or species. Since rat intestine is a classically studied target organ, these findings have additional relevance in receptor purification or other studies to characterize the receptor.

Animals↗

PubMed1986

Ethanol-induced cardiac hypertrophy: correlation between development and the excretion of adrenal catecholamines.

The progression of cardiac hypertrophy and the effects on adrenal medullary catecholamine content and release were determined in rats given ethanol, in conjunction with a supplementary diet, by gavage, every eight hours for periods up to 96 hours. Ethanol caused a marked depletion of adrenal medullary adrenaline content which fell to about 25 percent of control after the full time course. During this time, there were two- to fourfold increases in urinary noradrenaline content and five- to tenfold increases in urinary adrenaline. Cardiac hypertrophy, with increases in protein content and tissue weight of both ventricles, was evident at 24 hours of intoxication. By 96 hours of treatment these markers had increased more than 20% over control values. Proportional heart weight increases per day correlated significantly with daily urinary catecholamine excretion, providing support for the hypothesis that ethanol induced cardiac hypertrophy in the rat results from catecholaminergic stimulation, primarily of adrenal medullary origin.

Adrenal Glands↗

PubMed1986

Environmental specificity of tolerance to morphine-induced analgesia in a terrestrial snail: generalization of the behavioral model of tolerance.

Terrestrial snails, Cepaea nemoralis, develop tolerance to morphine-induced analgesia, such that after 7-9 days of treatment with morphine (10 mg/kg) their response latencies to an aversive thermal stimuli (38.5 degrees C) are not significantly different from those of untreated control animals. In Experiment A snails were rendered tolerant to morphine using either of two pre-injection cues (light and dark background brightness or color) and then assessed for morphine-induced alterations in thermal nociceptive responses in both environments. In Experiment B snails were made tolerant to morphine in the presence of one of two different thermal cues (a stressful temperature of 35 degrees C that is normally avoided or an ambient temperature of 22 degrees C) and then tested for morphine-induced alterations in nociceptive responses in both environments. In the two experiments tolerance to morphine-induced analgesia was displayed when snails were exposed to the pre-injection environmental cue normally associated with the administration of morphine, but not when exposed to the alternative pre-injection cue. These results demonstrate that various environmental factors (background colors or brightness as well as temperature cues and potentially thermal stress), can function as environmental specific cues for the development of tolerance to morphine-induced analgesia in molluscs, in a manner consistent with a behavioral mechanism of tolerance. Thus, these results suggest that environmental specificity of tolerance involving either classical (Pavlovian) conditioning or habituation may be a general phenomenon having an early evolutionary development and broad phylogenetic continuity.

Analgesia↗

PubMed1986

Food hoarding and ingestion in the deer mouse, Peromyscus maniculatus: selective responses to mu and kappa opiate agonists.

The feeding behavior of the deer mouse, Peromyscus maniculatus, includes food hoarding as well as ingestion. Administration of the prototypical mu opiate agonist, morphine sulfate, 1-20 mg/kg, produced over three hours a significant dose-dependent stimulation of hoarding by free feeding deer mice. The specific kappa opiate agonist, U-50,488H, 0.10-10 mg/kg, markedly increased ingestion without having any augmentatory effects on hoarding. The mixed mu and kappa opiate agonist, ketocyclazocine hydrochloride, 1-10 mg/kg, as well as various combinations of morphine sulfate and U-50,488H, augmented both hoarding and ingestion. Food restriction for 24 hr caused a significant, naloxone (1.0 mg/kg) reversible, increase in food intake. Food deprivation also modified the hoarding and ingestion responses of the deer mice to the mu and kappa opiate agonists, reducing the relative amounts of food that were hoarded. These results indicate that mu and kappa opioid systems are differentially involved in the mediation of various aspects of feeding. This also suggests that environmental factors, such as food restriction, can modify the relative roles of mu and kappa opioid systems in the expression of feeding behavior.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1986

Mu- and kappa-opiate agonists modulate ingestive behaviors in the slug, Limax maximus.

Administration of the prototypical mu opiate agonist, morphine sulphate, 1-10 mg/kg, produced over three hours a significant dose-dependent increase in the ingestive responses of free-feeding slugs, Limax maximus, although lower doses, 0.10 mg/kg, attenuated feeding. The mixed mu and kappa opiate agonist, ketocyclazocine hydrochloride, in the dose range 1.0-10 mg/kg, also induced significant increases in food consumption. With both of these opiates there was a latency of about 0.5 hr before initiation of feeding. The more specific kappa opioid agonist, U-50,488H, given over the dose range 0.10-1.0 mg/kg, produced a more potent increase in three hour food consumption by Limax, whereas a dose of 10 mg/kg produced a significant increase in ingestive responses for 3-4 hr after a 1-2 hr period of inactivity. The prototypic mu opiate antagonist, naloxone hydrochloride (1.0 mg/kg) blocked the feeding effects of morphine and ketocyclazocine and reduced the effects of U-50,488H. The delta antagonist, ICI 154,129, in a dose of 10 mg/kg, reduced the effects of morphine as well as decreasing food intake of free-feeding slugs. These results indicate that activation of differential opiate receptors in invertebrates has similar effects on feeding behavior as occur in mammals, suggesting early evolutionary development of opioid involvement in the control of feeding.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1986

FMRFamide: an endogenous peptide with marked inhibitory effects on opioid-induced feeding behavior.

The peptide FMRFamide (Phe-Met-Arg-Phe-NH2), which displays a broad phylogenetic distribution, is considered to have important regulatory influences on basic functions in invertebrates. Extensive FMRFamide-like immunoreactive neuropeptides have also been demonstrated in the mammalian central nervous system, suggesting a possible physiological role for these peptides in mammals. There is evidence that FMRFamide, and/or related neuropeptides, may modulate opioid-mediated responses. Intracerebroventricular (ICV) administrations of FMRFamide inhibit in a dose-dependent manner (0.01-10 micrograms) mu- (morphine) and kappa- (U-50,488H) opiate-induced feeding in the laboratory mouse. In deer mice, FMRFamide inhibits the display of exogenous opiate-induced components of natural feeding behavior, such as food hoarding and food ingestion. In addition, ICV administrations of FMRFamide also antagonize endogenous opioid-mediated, stress-induced feeding in mice. These observations suggest that FMRFamide, or FMRFamide-like peptides present in the mammalian brain, may have important roles in the control of opioid-mediated feeding.

Animals↗

PubMed1986

The influence of adrenal medullectomy on the development of ethanol-induced cardiac hypertrophy.

Cardiac hypertrophy was assessed in adrenal medullectomized and sham control rats given ethanol in a liquid diet mixture, intragastrically, in severely intoxicating doses at 8-h intervals for 48 and 96 h. The ethanol treatments produced increases of some 20% in wet and dry proportional heart weights in the control animals, but this rapid development of hypertrophy was less apparent in the medullectomized rats. Hearts of the medullectomized animals given ethanol were heavier than those of pair-matched controls given isocaloric maltose-dextrin in the diet mix. These increases were not statistically significant. The ethanol treatments produced, in addition, equivalent increases in the weight of the adrenal glands of both medullectomized and control animals. Medullectomy was evaluated by analysis of adrenal glands and urine samples for catecholamines. The majority of adrenals from the demedullated group had nondetectable amounts of catecholamines and minimal quantities were found in the remainder. Adrenaline was not detected generally in urine samples from this group. The adrenaline contents of adrenals from sham controls given ethanol were markedly reduced by the ethanol treatments, whereas the quantities in urine were many times greater than those from rats given maltose-dextrin. Urinary noradrenaline levels were increased in both control and medullectomized rats given ethanol. The results of this study identify that adrenal medullary catecholamines participate in the rapid development of cardiac hypertrophy that results from severe, continuing ethanol intoxication in the rat.

Adrenal Glands↗

PubMed1985

Differential opiate influences on food hoarding and intake in the deer mouse, Peromyscus maniculatus.

The feeding behavior of the deer mouse, Peromyscus maniculatus, includes food hoarding as well as ingestion. In this animal the mu opiate agonist, morphine, and the kappa opiate agonist, U-50, 488H, selectively stimulate food hoarding and ingestion, respectively. This suggests that mu and kappa opiate systems may differentially mediate primary components of natural feeding behavior.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1985

Exposure to nuclear magnetic resonance imaging procedure attenuates morphine-induced analgesia in mice.

Adult male mice exposed to a Nuclear Magnetic Resonance Imaging (NMRI) procedure during the mid-dark period and injected with morphine (10 mg/kg) failed to exhibit the normal nocturnally enhanced morphine analgesia response to a thermal stimulus that was displayed by mice exposed to a sham imaging procedure and treated with morphine (p less than .01). When tested during the mid-light period, animals exposed to the NMRI procedure and given morphine displayed attenuated analgesia levels relative to sham exposed mice (p less than .01) treated with morphine. However, the morphine induced analgesia was not totally abolished since the imaged mice still exhibited analgesia relative to saline treated mice (p less than .01). These results suggest that the magnetic and/or radio-frequency fields associated with the NMRI procedure alter both day- and night-time responses to morphine. These results may reflect magnetic field induced alterations in neuronal calcium binding and/or alterations in nocturnal pineal gland activity.

Analgesia↗

PubMed1985

Nocturnal feeding in the mouse--opiate and pineal influences.

Mice displayed daily rhythms in their basal and morphine-induced food intake, consuming significantly greater amounts of food at night. Non-invasive inhibition of the activity of the pineal gland by either exposure to a bright pulse of light or treatment with the L-amino-acid decarboxylase inhibitor, benserazide, reduced the elevated night-time food intakes. These effects on feeding were most evident on the first night the activity of the pineal was reduced. On subsequent nights light pulses had a diminished effect on basal and morphine-induced food intake. These results suggest that although the enhanced nocturnal food intake of mice may be modulated by pineal and opioid sensitive mechanisms, pineal activity is not essential for the expression of opioid-mediated feeding.

Animals↗

PubMed1985

The influence of opiate agonists on day-night feeding rhythms in young and old mice.

Daily rhythms of feeding behavior and responses to ketocyclazocine, morphine and naloxone were measured in young (1-2 months) and old (24-30 months) male CF-1 mice. All of the mice consumed more food at night than in the day-time, though this nocturnal peak was markedly reduced in the old animals, who consumed more in the day. The young mice also displayed a significant nocturnal enhancement in ketocyclazocine- and morphine-stimulated feeding. This day-night rhythm in ingestive responses was absent in the old mice. In comparison to the young mice, the opiate-stimulated food consumptions of the old animals were reduced at all times. Additionally, the old animals failed to show any day-night variations in the suppressive effects of naloxone on deprivation-induced food intake that were displayed by the young animals.

Aging↗

PubMed1985

The effects of aging on day-night rhythms of kappa opiate-mediated feeding in the mouse.

Day-night rhythms in feeding behavior and response to the specific kappa opioid agonist U-50,488H (0.10-10. mg/kg) were measured in young (1-2 months), mature (8-12 months) and old (24-30 months) male CF-1 mice. All the mice consumed more food at night than in the day-time, though this nocturnal peak was markedly reduced in old and mature animals. Young mice also displayed a significant, dose-related, nocturnal enhancement in U-50,488H-stimulated feeding. This day-night rhythm was reduced in mature animals and absent in old mice. In old mice, U-50,488H significantly stimulated feeding only after the high dose of 10 mg/kg. Additionally, old animals did not show the dose-dependent latency to initiation of feeding after administration which was observed in young mice and to a lesser extent in mature animals.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗