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Biomedical subjects

K Matthews

Publications and source records attributed to K Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1996

Retarded acquisition and reduced expression of conditioned locomotor activity in adult rats following repeated early maternal separation: effects of prefeeding, d-amphetamine, dopamine antagonists and clonidine.

Adult hooded rats exposed to a repeated maternal separation procedure during the neonatal period showed a blunted expression of locomotor hyperactivity conditioned to the presentation of the daily food ration. We have demonstrated that the expression of food-conditioned anticipatory hyperactivity is sensitive to the response-enhancing effects of systemic d-amphetamine (0.5; 1.0 mg/kg) and to the response-attenuating effects of the selective dopamine D2 antagonist sulpiride (8; 20 mg/kg), the selective dopamine D1 antagonist SCH 23390 (0.01; 0.022 mg/kg) and the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (5; 15 micrograms/kg) in a dose dependent manner. Animals from the early separation groups showed a reduced enhancement of activity in response to 0.5 mg/kg d-amphetamine and a greater attenuation of activity in response to 8 mg/kg sulpiride and 5 micrograms/kg clonidine. Female separated rats also exhibited an attenuated locomotor response to the unconditioned stimulant effects of 0.5 mg/kg systemic d-amphetamine. The experiments confirm that early maternal separation attenuates the response to conditioned appetitive cues in adult rats and implicate altered dopaminergic and noradrenergic function in the changes. It is possible that early maternal separation in the rat may offer a useful preparation for investigation of the neural substrates mediating affective development and affective psychopathology.

Adrenergic alpha-Agonists↗
PubMed1996

Repeated maternal separation of preweanling rats attenuates behavioral responses to primary and conditioned incentives in adulthood.

Early social experience has profound effects on a wide spectrum of behaviors and neurochemical correlates in the rat. Repeated separation of rat pups from their dam during the early neonatal period causes acute perturbation of neuroendocrine and physiological status. The chronic sequelae of repeated separations have not been studied as extensively as the acute responses. Altered social experience at a later developmental stage, postweaning isolation rearing, is known to induce enduring changes in the behavioral responses to reward and reward-related stimuli in maturity. We have evaluated the influence of repeated early maternal separation on the responses to both primary and conditioned incentives in mature rats. Separated animals showed enhanced weight gain, a blunted locomotor response to a novel environment and a blunting of the response to both negative and positive contrast effects. Female separated animals, but not males, exhibited a profound attenuation of the acquisition of a conditioned anticipatory locomotor response to the presentation of food. These data are discussed with respect to the putative involvement of ventral striatal dopamine systems in reward mechanisms and the potential utility of early maternal separation as an animal model of depression.

Animals↗
PubMed1996

Rewarding electrical brain stimulation: similar thresholds for Flinders Sensitive Line Hypercholinergic and Flinders Resistant Line Hypocholinergic rats.

Flinders Sensitive Line hypercholinergic rats, which exhibit augmented hypothermic responses to the cholinesterase inhibitor physostigmine and to the muscarinic agonist oxotremorine, have been proposed to represent a useful animal model for some aspects of human depression. With disturbance of reward processes considered to be a core feature of depression, the present studies were designed to investigate the neuropharmacology of brain stimulation-reward (BSR) in Flinders Sensitive Line (FSL) rats, Flinders Resistant Line (FRL) rats, and outbred control Sprague-Dawley rats. All animals were tested in a rate-free, current-threshold brain stimulation-reward paradigm, following acute challenges with the monoamine reuptake inhibitor cocaine, the dopamine D1 receptor antagonist SCH-23390, the cholinergic muscarinic antagonist scopolamine, and the serotonin reuptake inhibitor fluoxetine. Baseline BSR thresholds did not differ across the three groups. For all groups, cocaine lowered thresholds, SCH-23390 and scopolamine-elevated thresholds, while fluoxetine had no significant effect. Thresholds for the three groups were not differentially affected by pharmacological locomotor activity relative to outbred Sprague-Dawley controls. These results suggest that both Flinders lines exhibit behavioral differences from outbred control rats, but not with regard to reward processes as assessed by rewarding electrical stimulation of the lateral hypothalamus.

Animals↗
PubMed1996

Chronic mild stress and sucrose consumption: validity as a model of depression.

Sucrose consumption and preference were examined in rats subjected to a 6-week regimen of unpredictable mild stressors, after Willner et al. (11). These subjects were compared with groups exposed to: 1. only the food deprivation element of the stress protocol; or 2. the stress protocol without the food deprivation element. A control group was not exposed to stressors. Body weight and sucrose consumption were significantly reduced in stressed and food-deprived animals compared to the other 2 groups. These variables therefore appeared dependent on food deprivation and independent of other elements of the stress protocol. Neither sucrose consumption per gram body weight nor sucrose preference differed significantly among the 4 groups. These results indicate that food deprivation is not only necessary, but sufficient, to produce sucrose consumption deficits in rats. It is, therefore, likely that reduced sucrose consumption in stressed rats results solely from diminished body weight rather than exposure to the series of stressors. We conclude that sucrose consumption is not a valid index of reward responsiveness. Other measures (such as place-preference conditioning or intracranial self-stimulation threshold) should be evaluated also with respect to body weight change when considering the validity of stressor-based models of depressive disorder.

Animals↗
PubMed1995

Infrared spectrum of the cool brown dwarf Gl 229B.

Spectroscopic measurements of a cool brown dwarf, Gl 229B, reveal absorption features attributable to methane in the near infrared much like those of Jupiter. These features are not seen in any star. The presence of methane indicates that the surface temperature of Gl 229B is below 1000 kelvin. Features attributed to water vapor also indicate that Gl 229B is much cooler than any known star.

Extraterrestrial Environment↗
PubMed1995

Glycerol-3-phosphate dehydrogenase activity in human lymphocytes: effects of insulin, obesity and weight loss.

Insulin exposure stimulates an increase in glycerol-3-phosphate dehydrogenase (G3PDH) activity in isolated human lymphocytes that correlates to an increase in G3PDH mRNA and requires new protein synthesis. Synthetic diacylglycerol or phorbol ester can mimic the effect of insulin on G3PDH activity, suggesting that protein kinase C may be involved in regulation of G3PDH levels. In addition, lithium chloride, an inositol phosphate phosphatase inhibitor, and calcium uptake inhibitors can abolish insulin stimulation of G3PDH activity. For obese subjects in whom insulin resistance in vitro can be demonstrated, the extent of insulin stimulation of G3PDH activity is decreased compared to normal weight individuals, and treatment by a very low calorie diet restores insulin stimulation of G3PDH activity. Thus, insulin stimulation of G3PDH activity is dependent upon the metabolic state of the subject from whom the cells are obtained.

Diet, Reducing↗
PubMed1995

Sucrose consumption as an hedonic measure following chronic unpredictable mild stress.

The consumption of, and preference for, a rewarding 0.9% sucrose solution was examined in rats subjected chronically (8 wk) to a regimen of unpredictable mild stressors. Intake of sucrose was reduced in stressed animals compared to controls after 3 wk. However, correction for body weight changes revealed no significant difference in sucrose consumption between the groups. A comparison of the mean sucrose intakes of matched low-weight rats, with low weight a function of either immaturity or stress, failed to differentiate between the groups. Total sucrose consumption and total fluid intake correlated significantly with body weight of stressed animals and controls. Percentage preference for sucrose solution did not differ between controls and stressed animals. It is concluded that the validity and reliability of sucrose consumption as an hedonic measure within the context of exposure to chronic unpredictable mild stress must be questioned.

Animals↗
PubMed1995

Development of risk factors for cardiovascular disease among women from adolescence to older ages.

The development of risk factors for young adults to older ages for women has been evaluated in several studies. The increase in risk factor levels is related to age, weight gain, and diet. The levels of risk factors are related to extent of atherosclerosis, even at relatively young ages. The prevention of increase in risk factors is of primary importance for the future reduction of morbidity and mortality due to cardiovascular disease.

Adolescent↗
PubMed1994

Flinders resistant hypocholinergic rats exhibit startle sensitization and reduced startle thresholds.

Based on the hypothesis that depression involves a cholinergic-adrenergic neurotransmitter imbalance, a putative genetic animal model of depression has been developed by selectively breeding rats to exhibit hypocholinergia (Flinders Resistant Line--FRL), or hypercholinergia (Flinders Sensitive Line--FSL). The present experiments were designed to test the behavioral reactivity of these rats to external stimuli by measuring acoustic startle responses. The FRL rats exhibited lower startle thresholds compared to both FSL and control rats, while the FSL rats' startle thresholds were between those of controls and FRL rats. Despite the differences in thresholds, the three groups demonstrated similar levels of maximal startle reactivity to a high-intensity acoustic stimulus. With repeated stimulus presentations, FRL rats developed startle sensitization, a rarely observed phenomenon, while FSL and control rats exhibited habituation. There were no differences between the three groups in prepulse inhibition of startle. These results indicated that FRL rats exhibited interesting startle phenomena that are characteristic of certain psychiatric disorders, such as schizophrenia, post-traumatic stress disorder, and, potentially, depression.

Acetylcholine↗
PubMed1994

Climate change impact on distribution and abundance of wildlife species: an analytical approach using GIS.

An analytical approach to modelling the likely impact of climate change on the distribution and abundance of wildlife species is described using examples from Scotland. Data for present day distribution of wildlife and habitat are analysed using map data describing geographic variation in climatic factors. Climate data for the present day and under specified scenarios of change are themselves modelled within a GIS; climate modelling uses meteorological station data, climate change scenarios developed from GCMs and a variety of spatial interpolation techniques. The analytical procedure generates hypotheses defining ecological relationships between species distribution and climatic factors (monthly, seasonal and annual data). These relationships are then used to model the distribution of the species directly from climate and predict impacts of climate change. The analysis takes account of both direct impacts of climate on wildlife and indirect effects manifested through habitat response to climate change. The analytical procedure is implemented as a generic tool for inductive spatial analysis in GIS.

Journal Article↗
PubMed1994

Electrostatic forces contribute to interactions between trp repressor dimers.

The trp repressor of Escherichia coli (TR), although generally considered to be dimeric, has been shown by fluorescence anisotropy of extrinsically labeled protein to undergo oligomerization in solution at protein concentrations in the micromolar range (Fernando, T., and C. A. Royer 1992. Biochemistry. 31:3429-3441). Providing evidence that oligomerization is an intrinsic property of TR, the present studies using chemical cross-linking, analytical ultracentrifugation, and molecular sieve chromatography demonstrate that unmodified TR dimers form higher order aggregates. Tetramers and higher order species were observed in chemical cross-linking experiments at concentrations between 1 and 40 microM. Results from analytical ultracentrifugation and gel filtration chromatography were consistent with average molecular weight values between tetramer and dimer, although no plateaus in the association were evident over the concentration ranges studied, indicating that higher order species are populated. Analytical ultracentrifugation data in presence of corepressor imply that corepressor binding destabilizes the higher order aggregates, an observation that is consistent with the earlier fluorescence work. Through the investigation of the salt and pH dependence of oligomerization, the present studies have revealed an electrostatic component to the interactions between TR dimers.

Bacterial Proteins↗
PubMed1994

Suicide in Scotland 1988-1989. Psychiatric and physical morbidity according to primary care case notes.

BACKGROUND: The aim was to identify the amount of psychiatric and physical morbidity identified in suicide victims prior to death. METHOD: A survey was made of primary care records of Scottish suicide victims in the years 1988 and 1989. RESULTS: Less morbidity was encountered than in previous studies. Single persons and persons from lower socio-economic groups were less likely to have a diagnosis of depression. No association was found between physical and psychiatric morbidity. Depressed single persons and depressed persons from lower socio-economic groups were less likely to receive antidepressants. GPs prescribed lower dosages of antidepressants than psychiatrists. Patients receiving antidepressants were more likely to die by drug overdose. CONCLUSIONS: There are groups in whom depression may be being overlooked and others in whom depression could be treated more vigorously. There are risks in prescribing antidepressants which are potentially fatal in overdose.

Alcoholism↗
PubMed1994

One year experience of elderly hypertensive patients with isradipine therapy.

This is the first report of long-term use (one year) of isradipine, a new dihydropyridine calcium channel blocker, in the treatment of elderly patients with essential hypertension. Patients completing a three month, double-blind, multicentre study comparing isradipine to hydrochlorothiazide (HCTZ) were eligible to enroll in this open-label, continuation study. At initial baseline, patients were at least 60 years of age and had DBP from 95 mmHg to 120 mmHg. Patients were titrated when necessary every two weeks with isradipine, 5 mg to 15 mg once daily or 2.5 mg to 10 mg twice daily, to maintain sitting DBP < or = 90 mmHg. HCTZ, 12.5 mg to 50 mg once daily, could be added for better BP control. A total of 136 patients completed the one year, open-label phase. One hundred and fourteen patients (84%) received isradipine as monotherapy (mean dose, 9.7 mg/day); 22 received concomitant HCTZ therapy at one year. Reduction in DBP was significant and similar among all age groups and races (mean change of -19 mmHg). Reduction in SBP was similar among all age groups. Ninety-four per cent of those receiving isradipine monotherapy achieved BP control during the last four months of treatment. Twenty-six patients (16%) withdrew from the study: 11 (7%) had adverse reactions (one with headache, two with pedal oedema, eight with other problems); 11 (7%) had nondrug-related problems; and in four (2%), the drugs were ineffective. Based on these observations, isradipine is a well-tolerated, safe and effective agent for long-term BP control in elderly patients with essential hypertension.

Aged↗
PubMed1994

Role of doctors in the prevention of suicide: the final consultation.

BACKGROUND: It is generally assumed that people committing suicide see their doctor shortly before their death, and consequently that enhancing doctors' psychiatric knowledge and interview skills might help prevent some suicides. AIM: A study was undertaken to determine the nature and timing of final contacts with medical practitioners by people committing suicide. METHOD: Adults dying by suicide in Scotland during 1988-89 were identified by the General Register Office for Scotland and their primary care case notes studied. RESULTS: Within this national sample, medical contact near to the time of the suicidal act was rare, except for those individuals who had a previous psychiatric history. CONCLUSION: These data suggest that medical practitioners, particularly those working in primary care, are not failing to detect and intervene in significant numbers of preventable suicides. Consequently, the likelihood of implementing successful suicide prevention strategies based within primary care is open to question. Greater awareness of the risk of eventual suicide in those with a previous history of psychiatric disorder may contribute to any future reduction in suicide rates.

Adolescent↗