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Biomedical subjects

M Hirst

Publications and source records attributed to M Hirst.

At least 73 records · Page 4Linked to original sources

The effects of opioid and FMRF-amide peptides on thermal behavior in the snail.

Administration of methionine-enkephalin, beta-endorphin or, as previously shown, the opiate agonist, morphine sulfate (0.10-10.0 micrograms per snail), resulted in significant dose-dependent increases in the latency of thermal (40 degrees C hot plate) avoidance behavior of the terrestrial snail, Cepaea nemoralis. The analgesic effects could be blocked by the opiate antagonist, naloxone, as well as by the non-opioid peptides, FMRF-amide and YGG-FMRF-amide. When administered by themselves the FMRF-amide peptides had significant bimodal effects either decreasing (0.10 and 10.0 micrograms) or increasing (1.0 micrograms) the latency of the response to the thermal stimulus. These results indicate that opioid and FMRE-amide peptides may be involved in the determination of thermal behavior in the snail. They also suggest that FMRF-amide peptides may function as endogenous modulators of opioid activity.

Animals↗

The influences of ethanol and other factors on the excretion of urinary salsolinol in social drinkers.

Salsolinol, a substance that may participate in the development of alcoholism, has been identified in urine and other biological samples from alcoholics. Differentials have been observed between alcoholics and controls. Salsolinol forms when dopamine reacts with acetaldehyde, which may exist in higher concentrations in the blood of alcoholics after alcohol ingestion. Hence, it was postulated that there is a relationship between level of social drinking and the elaboration of salsolinol. Salsolinol is also found in certain food and beverage products. Eighty volunteers, balanced for gender, social drinking level, ethanol dose administered and experimental diet provided urine samples 90 minutes and three hours after ethanol was consumed. Salsolinol levels were analysed in urine using high performance liquid chromatography. A 24 hour carryover effect was observed. Diet, ethanol dose and social drinking level had main and interactive effects on excreted quantities of salsolinol. Gender, situational stress and cigarette smoking had minor if any influence on salsolinol excretion. While there was no evident difference in amounts of salsolinol excreted by light and heavy drinkers in the absence of external sources of salsolinol, heavy social drinkers excreted less salsolinol than did light drinkers after consuming a "salsolinol-enriched" diet, suggesting that they differ in some aspect of absorption, distribution, or metabolism of salsolinol after drinking ethanol. Accordingly, studies that attempt to determine whether salsolinol has any relationship to drinking behaviour in humans should be particularly concerned with salsolinol that occurs in exogenous sources.

Adult↗

FMRFamide, a putative endogenous opiate antagonist: evidence from suppression of defeat-induced analgesia and feeding in mice.

Social conflict and defeat in mice leads to an activation of endogenous opiate systems. The effects of intracerebroventricular administration of the peptide FMRFamide (Phe-Met-Arg-Phe-NH2) and the opiate antagonist naloxone, on aggressive encounters, defeat-induced analgesia and defeat-induced feeding were examined in male mice. Both substances reduced the number of bites required to cause defeat in subordinate mice during aggressive encounters, as well as suppressing the subsequent defeat-induced analgesia. Administration of FMRFamide or naloxone also reduced defeat-induced feeding. These results indicate that FMRFamide (or FMRFamide-like neuropeptides) may function as endogenous opioid antagonists.

Analgesia↗

PLG and FMRFamide--endogenous peptides with marked inhibitory effects on opioid-induced feeding.

Social conflict and defeat in mice leads to an activation of endogenous opiate systems and the display of marked feeding behavior. Intraperitoneal administrations of prolyl-leucyl-glycinamide (PLG 0.01-10 mg/kg) leads to a dose-dependent inhibition of defeat-induced feeding that is analogous to that obtained after treatment with either the endogenous peptide FMRFamide (Phe-Met-Arg-Phe-NH2), or the prototypic opiate antagonist, naloxone. These results suggest that PLG, and FMRFamide, or related small peptides may function as endogenous antagonists of opioid-induced feeding.

Animals↗

Opioid systems and feeding in the slug, Limax maximus: similarities to and implications for mammalian feeding.

Substantial evidence is accumulating to implicate opioid systems in the regulation of behavioral and physiological functions in invertebrates in a manner analogous to that observed in vertebrates. This communication reviews opiate involvement in the mediation of the ingestive behaviors of the terrestrial slug, Limax maximus. The similarities to and implications for opioid modulation of mammalian feeding are considered.

Animals↗

Inhibitory influences of FMRFamide on morphine- and deprivation-induced feeding.

Intracerebroventricular administration of 0.01-1.0 microgram of the peptide FMRFamide (Phe-Met-Arg-Phe-NH2) to mice reduced morphine-induced feeding. Administration of FMRFamide also inhibited feeding induced by a 24-hour period of food deprivation. These results suggest that FMRFamide or FMRFamide-like neuropeptides play an important role in the control of opioid-mediated feeding.

Animals↗

Evidence for the activation of the endogenous opiate system in hamsters infected with human blood flukes, Schistosoma mansoni.

Nociceptive thresholds were investigated in golden hamsters infected with the human blood fluke, Schistosoma mansoni. Increases in thermal thresholds suggestive of analgesia were evident by 20-25 days of infection. These increased further during a 40-42 day period. The altered responses were suppressed by the opioid antagonist naloxone. Non-invasive inhibition of the activity of the pineal gland by exposure to light also reduced nocturnal analgesia in schistosome infected animals. Naloxone antagonism and pineal inhibition of morphine- induced analgesia was obtained similarly in control, uninfected animals. Taken together, these findings suggest strongly that infection with S. mansoni results in a chronic activation of the endogenous opiate system.

Analgesia↗

Social conflict activates opioid analgesic and ingestive behaviors in male mice.

The activation of endogenous opioid mechanisms and their subsequent effects on rodent behavior and physiology has usually been characterized following artificial stress. In this study the more naturalistic stress arising from social conflict between male mice was used to investigate the involvement of opioid systems in post-conflict analgesic and ingestive behaviors. Both the aggressive encounters and the subsequent defeat experience resulted in marked analgesia and the induction of ingestive behaviors. Feeding and drinking responses were analogous to those observed after administrations of either the endogenous opioid peptide, beta-endorphin, or the exogenous opioid agonist morphine. The ingestive behaviors following defeat or central opiate administration were blocked by the opiate antagonist naloxone. The present results support the hypothesis of a direct activation of the endogenous opiate system following social conflict.

Aggression↗

Occupational exposure to cyclophosphamide.

Several lines of research have demonstrated the risk of occupational exposure of health-care personnel to anticancer drugs. Urine samples from two nurses working in a cancer clinic were analysed for cyclophosphamide (CP) by gas chromatography after they had prepared the drug for treatment. Since the drug might be absorbed through the skin, urine samples from five volunteers were also examined after a solution of CP had been applied topically to the cubital fossa area. Variable quantities of intact CP were identified in samples from the volunteers collected over 24 h, but in most cases the drug was evident only in urine samples given more than 6 h after application. CP was found in several urine samples from the nurses, but the quantities of CP in these samples were not related to the amounts of drug handled. The identity of CP was confirmed by gas-chromatography/mass-spectrometry. CP appeared sooner in the urine samples from the nurses than in those from the volunteers, suggesting a faster route of absorption, perhaps through inhalation of aerosols generated during dissolution of the drug. These findings suggest that the increased levels of mutagenicity observed in urine samples of nurses who worked on oncology wards might have arisen, in part, from metabolites of CP.

Adult↗

The presence of an opioid system mediating behavioral thermoregulation in the terrestrial snail, Cepaea nemoralis.

Administration of the opiate agonist, morphine sulfate (0.1-10 micrograms per snail) resulted in a significant dose- and time-dependent increase in the temperatures selected by the terrestrial snail, Cepaea nemoralis, in a thermal gradient. These thermoregulatory effects could be blocked and reversed by naloxone hydrochloride, with the opiate antagonist by itself (1 and 10 micrograms) causing a significant decrease in preferred temperatures. After 6-10 days of daily administration of morphine, Cepaea displayed tolerance, the effects of morphine decreasing and thermal preferences becoming similar to those of saline-treated individuals. These results suggest that an opioid system is involved in the control of thermoregulation in snails, in a manner that is similar to that shown by vertebrates.

Animals↗

Opioid-induced feeding in the slug, Limax maximus.

Administration of the opioid agonist, morphine (1 and 10 mg X kg-1), resulted in significant, dose-dependent increases in the ingestive responses of food-deprived slugs, Limax maximus, and in the initiation of feeding in satiated animals. These effects could be blocked by the opiate antagonist, naloxone (1 mg kg-1), with naloxone by itself causing a significant decrease in the feeding of food-deprived slugs. These results suggest that opiates are involved in the control of the feeding behavior of Limax.

Animals↗

Opiates influence behavioral thermoregulation in the curly-tailed lizard, Leiocephalus carinatus.

Low doses of the opioid agonist, morphine (1-3 mg kg-1), significantly increased the behaviorally selected body temperatures of the curly-tailed lizard, Leiocephalus carinatus. A higher dose of morphine (10 mg kg-1) resulted in an initial behavioral hyperthermia that was followed by a significant decrease in preferred temperatures and a subsequent behavioral hypothermia which declined to control levels within 3-4 hr. These effects could be blocked and reversed by the opiate antagonist, naloxone, with naloxone (1 and 10 mg kg-1) by itself causing significant dose-dependent decreases in preferred temperatures. These morphine and naloxone induced changes occurred regardless of initial body temperatures. These results suggest that opiates are involved in the control of behavioral thermoregulation in lizards.

Animals↗

Magnetic fields abolish the enhanced nocturnal analgesic response to morphine in mice.

Mice given morphine displayed diel rhythms in the latency of their behavioral response to placement on a hot plate, there being a several fold increase in their nocturnal reaction times. Exposure to a rotating magnetic field eliminated the day-night analgesia rhythms, reducing over 5-10 days the enhanced nocturnal latencies to those found during the day. The attenuation returned to normal nocturnal levels several days after removal of the rotating magnetic field and could be subsequently re-established by reapplication of the magnetic field condition. It is suggested that these changes in analgesia may reflect alterations in the activity of the pineal gland during exposure to magnetic fields.

Analgesia↗

Adrenal and urinary catecholamines during and after severe ethanol intoxication in rats: a profile of changes.

Adrenal and urinary levels of adrenaline and noradrenaline were determined in rats subjected to severe ethanol intoxication for periods of up to 96 hours, in rats undergoing withdrawal and in a post-withdrawal period, and in controls. Adrenaline and noradrenaline content of adrenal glands fell markedly to less than eight and twenty percent, respectively, after four days of intoxication. Noradrenaline content, but not adrenaline content, had recovered after a subsequent four day period of recovery. The depletion in adrenal catecholamine levels was coincident with increases in urinary adrenaline and noradrenaline levels over the first 48 hours of intoxication. Urinary catecholamine levels remained higher than control values for the next 48 hours of intoxication. Adrenal glands were larger after 12 hours of intoxication, although there was no increase in dry weight. At later times adrenal enlargement was associated with increased dry weight and protein content. This increase in mass was found to be of cortical origin. These results demonstrate that severe ethanol intoxication promotes an intense stimulation of the rat adrenal gland with enhanced synthesis and release of catecholamines, and cortical hypertrophy.

Adrenal Glands↗

Aging and daily rhythms of analgesia in mice: effects of natural illumination and twilight.

Day-night rhythms in aversive thresholds and morphine-induced analgesia were assessed in young (1-3 months) and old (22-30 months) male mice exposed to natural summer (43 degrees N lat.) lighting using a hot-plate technique. In both age groups peak aversive thresholds and morphine-induced analgesia were present at night, with significantly reduced response times in the day. Response times increased during the course of the day with maximum increases in aversive thresholds and analgesia occurring during the decreasing light levels of dusk. Maximum decreases in the nocturnal response times occurred during the increasing light levels of dawn. The old mice displayed significantly lower nocturnal aversive thresholds and morphine-induced analgesia, as well as less pronounced patterns of change in response times during the dawn and dusk twilight lighting transitions. No significant effects of age were evident during the day-time.

Aging↗

Age and day-night changes in clonidine-induced analgesia in mice.

Administrations of clonidine hydrochloride (0.1, 1.0 mg/kg) to young, mature, and old mice influenced their response time on a thermally aversive surface (50 degrees C) in an age-dependent manner. This analgesic effect was of short duration. During daytime measurement periods, young and mature mice showed significantly greater analgesic responses than did the old animals. Although all animals were able to perform the appropriate paw-licking response, the old mice displayed tremors and locomotor disturbances after receiving clonidine. These effects were not seen in the younger groups. Both the young and mature animals showed a substantial enhancement of their analgesic responses after receiving clonidine at night, whereas a significant but much reduced nighttime increase in antinociceptive effect was seen in old animals. Yohimbine, but not prazosin, inhibited clonidine-induced analgesia in young animals. Old mice given combinations of clonidine and these adrenergic antagonists showed elevations in response times, accompanied by severe behavioural changes.

Age Factors↗