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Biomedical subjects

M L Thompson

Publications and source records attributed to M L Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Relationship of plasma and brain concentrations of caffeine and metabolites to benzodiazepine receptor binding and locomotor activity.

CD-1 mice were treated with caffeine-sodium benzoate solution (caffeine doses: 0, 5, 15 or 30 mg/kg i.p.) to determine plasma and brain concentrations, effects on benzodiazepine receptor binding based on specific uptake of a high affinity ligand, and locomotor activity. There was a linear relationship between caffeine dose and mean brain or plasma concentrations, but concentrations varied considerably at any given dose. There were also linear relationships between plasma and brain concentrations of caffeine and each metabolite, with caffeine itself having the greatest brain:plasma uptake ratio. Benzodiazepine receptor binding was determined based on uptake of the benzodiazepine receptor ligand [3H]Ro15-1788, 3 microCi i.v. given 40 min after caffeine (30 mg/kg). Nonspecific binding was measured in animals pretreated with saturating doses of clonazepam. Specific uptake (measured by subtracting nonspecific from total [3H] Ro15-1788 uptake) increased significantly with caffeine as opposed to vehicle treatment in the cortex, hippocampus and hypothalamus. Brain caffeine concentrations associated with enhanced uptake were between 11 to 17 micrograms/g. Total locomotor activity and activity at 60 min, measured by an infrared sensor system, increased progressively with brain caffeine concentrations when comparing the following groups: 0, 2 to 9 micrograms/g of brain and 9 to 20 micrograms/g. Animals with brain concentrations exceeding 20 micrograms/g showed a decline in both measures but activity was significantly greater than placebo. In conclusion, brain caffeine concentrations between 9 to 20 micrograms/g are associated with increases in specific ligand uptake and motor activity.

Adenosine↗
PubMed1988

Modulation of benzodiazepine receptor binding in mouse brain by adrenalectomy and steroid replacement.

Adrenal steroids alter neuronal excitability in the central nervous system (CNS), and evidence from in vitro studies indicates that at least some of these effects are mediated by the GABAergic system. Benzodiazepine receptor binding, among other sites on the GABA complex, has been implicated in steroid-induced alterations in the CNS. To investigate the modulation of benzodiazepine receptor binding by adrenal steroids, we examined receptor binding determined by an in vivo technique in mice after adrenalectomy, hypophysectomy and after replacement with several naturally occurring and synthetic steroids. Benzodiazepine receptor binding was substantially augmented in cortex, hypothalamus, and hippocampus in mice 1 week after adrenalectomy, and these increases appeared to be due to increased receptor number rather than changes in apparent affinity. Similar results in cortex were found after hypophysectomy. Replacement with physiologic, but not lower doses, of corticosterone reversed the changes induced by adrenalectomy. Chronic treatment with deoxycorticosterone also returned binding to control values, but chronic administration with dexamethasone, aldosterone and dihydroprogesterone did not alter binding after adrenalectomy. Adrenalectomy did not alter non-specific binding or GABA concentrations in cortex, and delivery of radioligand did not appear to be affected. These results indicate that adrenal steroids modulate benzodiazepine receptor binding in vivo, perhaps via the CR subtype of corticosteroid receptors. The steroid-benzodiazepine interaction may be especially important in the stress response.

20-alpha-Dihydroprogesterone↗
PubMed1988

Analgesia in defeated mice: evidence for mediation via central rather than pituitary or adrenal endogenous opioid peptides.

Mice subjected to defeat in a social conflict paradigm display an analgesic response that is apparently mediated by endogenous opioids. It is blocked by naloxone and shows full cross-tolerance to and from morphine. The present study investigated the contribution of sources of endogenous opioids outside of the central nervous system, namely the pituitary and adrenal glands. Treatment known to enhance (metyrapone pretreatment), reduce (2% saline in the drinking water) or block (dexamethasone pretreatment) the release of beta-endorphin from the anterior pituitary did not affect the display of analgesia in defeated mice. Similarly, treatments known to enhance (reserpine pretreatment) or block release of enkephalins (removal of the adrenals or hexamethonium pretreatment) from the adrenal medulla also failed to influence defeat-induced analgesia in the expected manner. If anything, adrenalectomy enhanced and reserpine pretreatment suppressed the analgesic response to defeat. The data are discussed in terms of providing evidence that defeat-induced analgesia is mediated primarily by endogenous opioids released and acting within the central nervous system.

Animals↗
PubMed1987

Rapid increase in brain benzodiazepine receptor binding following defeat stress in mice.

Defeat stress in mice, a model of social stress, increases benzodiazepine receptor binding as measured by specific [3H]Ro15-1788 binding in vivo, but not by [3H]flunitrazepam binding in vitro. This increase occurs rapidly, by 20 min following exposure to stress, and resolves by 60 min. Increased benzodiazepine receptor binding is observed in the cerebral cortex, cerebellum and hypothalamus, and appears to be due to an increase in receptor number rather than apparent affinity. The stress-induced increase in central benzodiazepine receptors is decreased in a dose-dependent fashion by lorazepam, a benzodiazepine agonist, but not by the receptor antagonist Ro15-1788. The stress-induced increase in benzodiazepine receptors is also blocked by adrenalectomy and is restored by corticosterone replacement.

Adrenalectomy↗
PubMed1985

Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice.

In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 micrograms) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 micrograms) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat.

Analgesia↗
PubMed1984

Sex and strain differences in response to cocaine.

After pretreatment with phenobarbital, female B6AF1 mice showed considerably higher serum glutamic oxaloacetic transaminase (SGOT) elevations and more periportal necrosis from a single injection of cocaine than males. This sex difference was androgen dependent. Castration or treatment with flutamide made males respond like females, while testosterone made females behave like males. There was no significant sex difference in enzymes of cocaine metabolism. When the mice were induced by exposure to pine bedding, males showed higher SGOT elevations and more centrilobular necrosis after cocaine than females. In this case, the sex difference could be attributed to increased levels of cytochrome P-450 and cocaine N-demethylase in liver microsomes. BALB/cBy mice on pine bedding showed much less liver damage from cocaine than B6AF1 mice, but they were more sensitive to norcocaine and N-hydroxynorcocaine. This difference was correlated with low levels of cocaine N-demethylase in the BALB/cBy mice. Liver microsomes from phenobarbital-induced BALB/cBy mice had less norcocaine N-hydroxylase activity than those from B6AF1 mice. These studies demonstrate that the pattern of sex and strain differences in liver damage from cocaine depends on the inducing agent and can be related to a large extent to the microsomal enzymes induced by that agent.

Aging↗
PubMed1984

Effects of naloxone and naltrexone on drug-induced hypothermia in mice.

The hypothermia produced by injecting apomorphine into mice was potentiated by morphine; it was antagonized by haloperidol, by naloxone and by naltrexone. The hypothermic responses to morphine, chlorpromazine and ethanol were also blocked by naltrexone. However, naltrexone potentiated the hypothermic response to pentobarbital. Tolerance to morphine, produced by subcutaneous implantation of a morphine pellet, was accompanied by cross-tolerance to apomorphine-induced hypothermia. Animals made tolerant to apomorphine were not tolerant to morphine-induced hypothermia. The dopamine supersensitivity resulting from chronic treatment with haloperidol potentiated the hypothermic response to apomorphine but not to morphine. These results suggest that endogenous opioids may serve as mediators in the control of thermoregulation by dopamine.

Animals↗
PubMed1984

Alcohol education in schools: toward a lifestyle risk-reduction approach.

This article calls for a refocusing of alcohol education to facilitate the adoption of low-risk lifestyle choices regarding decisions about abstinence and quantity and frequency of alcohol use. Five goals are presented as a focal point for lifestyle risk-reduction education about alcohol. It is essential that research and education activities become more focused on the link between the quantity-frequency of alcohol use and alcohol-related problems, and on the information and attitudes that support low-risk versus high-risk A/Q/F choices.

Adolescent↗
PubMed1982

Opioid-like analgesia in defeated mice.

Mice exposed to repeated attacks by other mice showed decreased nociception in response to radiant heat focused on their tails. This form of analgesia was blocked by centrally acting opiate antagonists and was not observed in morphine-tolerant mice; furthermore, mice repeatedly subjected to defeat. Mice of the CXBK strain, which respond weakly to morphine, displayed only moderate analgesia following defeat. These findings suggest that endogenous opioid-mediated analgesic mechanisms are readily activated by situations involving biologically significant forms of stress, such as defeat.

Aggression↗
PubMed1977

Ipratropium bromide: mucociliary clearance rate and airway resistance in normal subjects.

The effect of ipratropium bromide, a new anticholinergic drug, on the rate of clearance of secretions from the lung and on airways resistance was investigated in 12 healthy subjects in a double-blind cross-over trial with placebo and a control run without aerosol. Before taking the drug the subjects inhaled uniform 5 micrometer tracer particles of polystyrene in which 99mTc had been unleachably incorporated. The initial depth of deposition and the rate of clearance of the particles were obtained from serial gamma counts made externally to the chest over six hours. The difference between drug, placebo and control runs in the deposition patterns of the tracer particles and their subsequent rates of clearance were not significant. The drug treatment resulted in statistically significant falls in specific airway resistance at 1, 2, 3 and 6 hours (P less than 0.02). There was no objective or subjective evidence of side effects from the drug.

Aerosol Propellants↗
PubMed1976

Effects of adrenalectomy on the sexual behaviour of castrated and intact BDF1 mice.

Two experiments investigate the effects of adrenalectomy on the capacity of male mice of the BDF1 genotype (C57B1/6Fa male X DBA/2 female) to retain sexual behaviour following castration. Adrenalectomy is without effect and it is suggested that androgens can play no part in the maintenance of sexual behaviour in these castrates.

Adrenalectomy↗
PubMed1976

Postcastration retention of sexual behaviour in the male BDF1 mouse: the role of experience.

Male BDF1 mice (the F1 progeny of a cross between C57BL/6 females with DBA/2 males) show a remarkable retention of sexual behaviour following castration. Two experiments were conducted to describe in detail the postcastration copulatory performance of the BDF1 male mouse and to determine to what extent such performance is influenced by experience prior to castration. Experiment I found that castration leads to significant increases in the number of mounts and intromissions needed to reach ejaculation, and to a significant increase in ejaculation latency. Experiment II found that although precastrational sexual experience is not essential for the performance of the ejaculatory reflex after castration, it does influence the frequency of its occurrence. Furthermore, type of post-weaning social experience influenced the display of ejaculatory behaviour by non-experienced castrates, as those with female social experience were superior to those with social experience with males or no social experience. The interactions of experience, hormones and genotype in the control of sexual behaviour in the BDF1 male are discussed.

Animals↗