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J R Walters

Publications and source records attributed to J R Walters.

At least 109 records · Page 6Linked to original sources
PubMed1984

Single unit responses of substantia nigra pars reticulata neurons to apomorphine: effects of striatal lesions and anesthesia.

Many of the behavioral consequences of dopamine system activation are thought to be mediated by substantia nigra pars reticulata output pathways. Extracellular, single unit recording studies were conducted to determine how i.v. administration of the dopamine agonist, apomorphine, affects the activity of these pars reticulata neurons. Results revealed that a 320 micrograms/kg dose of the drug, considered sufficient to stimulate striatal postsynaptic dopamine receptors, caused highly variable changes in reticulata cell firing. Cells exhibited increases, decreases, or no changes in firing. Many cells also displayed marked minute to minute changes in firing. This non-uniform pattern of responses was not related to state of consciousness since similar responses were observed in both chloral hydrate-anesthetized as well as conscious, paralyzed rats. Both the increases and decreases could be reversed by subsequent administration of haloperidol. The variable responses to apomorphine were reduced but not totally prevented by striatal kainic acid lesions, suggesting that changes in striatonigral transmission may account for some but not all of the firing changes which were observed. A lower dose of apomorphine (20 micrograms/kg), thought to act primarily at dopamine cell autoreceptors, had little effect on reticulata cell firing and did not modify the variable responses normally observed after the higher dose. These results contrast strikingly with the consistent excitatory responses to apomorphine which have previously been observed in the globus pallidus and suggest that complex or multiple indirect effects of the drug may contribute to the varied reticulata responses.

Anesthesia, General↗
PubMed1984

Dopamine agonists increase pallidal unit activity: attenuation by agonist pretreatment and anesthesia.

Intravenous administration of a single bolus dose of 1 mumol/kg of the dopamine agonists, pergolide and lisuride, caused marked increases in the unit activity of globus pallidus neurons in awake, paralyzed, locally anesthesized and artificially respired rats. These agonist effects were similar to those observed after administration of 1 mumol/kg apomorphine to awake, paralyzed rats; in rats anesthetized with chloral hydrate, however, responses to apomorphine were markedly attenuated. Subsequent administration of haloperidol reversed the effects of pergolide and pretreatment with haloperidol blocked the effects of lisuride. LSD (1 mumol/kg i.v.) did not effectively stimulate pallidal neuronal activity, suggesting that the ability to stimulate pallidal firing rates correlates better with dopamine, as opposed to serotonin, agonist potency. The ability of a non-excitatory dose of apomorphine to attenuate responses of pallidal neurons to a normally excitatory 1 mumol/kg dose of this agonist administered subsequently, was reconfirmed. Pretreatment with this 'priming' dose of apomorphine also attenuated the rate increases produced by d-amphetamine (8.7 mumol/kg) and enhanced the rate inhibitory effects of haloperidol. The 'priming' effect appears related to the dopamimetic effects of apomorphine; a non-excitatory dose of a second dopamine agonist, lisuride (0.07 mumol/kg i.v.), similarly blocked the effect of excitatory doses of lisuride (1 mumol/kg i.v.) on pallidal activity.

Action Potentials↗
PubMed1984

Characterization of the vitamin D-dependent Ca2+-binding sites in rat intestinal Golgi-enriched membrane fractions.

Rat intestinal Golgi-enriched membrane fractions take up Ca2+ by a vitamin D-dependent process that has been shown to recover within 15 min of repletion of vitamin D-deficient animals with intravenous 1,25-dihydroxycholecalciferol. The present paper reports studies characterizing the Ca2+-binding sites of these membrane fractions. Equilibrium binding of Ca2+ at concentrations between 5 and 400 microM showed significant decreases at all concentrations in membranes derived from vitamin D-deficient animals when compared with normal control-diet-fed animals. The predominant class of binding sites had a relatively high affinity for Ca2+ (KD approx. 3 microM). Vitamin D-deficiency did not change the affinity of this class of site, but decreased the number from 347 +/- 26 to 168 +/- 50 nmol of Ca2+ bound/mg of protein (means +/- S.D.). Mg2+ inhibited binding only at low Ca2+ concentrations, and the characteristics of this binding suggested positive co-operativity between two binding sites. Equimolar concentrations of Zn2+, La3+, Pb2+ and Mn2+ inhibited Ca2+ binding by over 50%. Increased ionic strength decreased Ca2+ binding by no more than half. Binding was maximal at pH 7.5 and half-maximal at pH 6.3. The large number of binding sites with relatively high affinity for Ca2+ suggests that it is unlikely that this binding is to any specific protein or to non-specific sites present on many proteins, and that the most likely sites are lipid molecules.

Animals↗
PubMed1984

Relationship of non-esterified fatty acids to vitamin D-dependent Ca2+ binding by rat intestinal Golgi-enriched membrane fractions.

Ca2+ binding and concentrations of non-esterified fatty acids and phospholipids were compared in membrane fractions of rat small intestine. These fractions differed in density and were enriched for galactosyltransferase activity, a Golgi-membrane marker. Ca2+ binding was highest in the Golgi subfraction with the least density, as were the concentrations of both non-esterified fatty acids and phospholipids; galactosyltransferase activity was distributed differently. The large amount of non-esterified fatty acids was sufficient to account for a 2:1 complex of fatty acid-Ca2+. In vitamin D-deficient animals, the yield of protein in the lightest subfractions was decreased, but Ca2+ binding per mg of protein was further decreased to about 60%. In Golgi fractions from vitamin D-deficient animals, Ca2+ binding and the concentration of non-esterified fatty acids were decreased in parallel, but phospholipids were not significantly changed. There was a close correlation between Golgi Ca2+ binding and non-esterified fatty acid concentrations (r = 0.89; P less than 0.001). Non-esterified fatty acids, which are unusually prevalent in these membrane fractions, are likely to be the binding sites that account for this vitamin D-dependent Ca2+ uptake.

Animals↗
PubMed1984

Effect of alcohol withdrawal on blood pressure, plasma renin activity, aldosterone, cortisol and dopamine beta-hydroxylase.

Sixty-five alcoholic patients admitted for detoxification had blood pressure, withdrawal symptoms, plasma cortisol (PC) and plasma aldosterone (PA) levels, plasma renin activity (PRA), and serum dopamine beta-hydroxylase (DBH) levels measured on the first and fourth days after admission. On the morning after admission blood pressure was elevated (greater than 140/90) in 32 patients (49%) and was 160/95 mmHg or more in 21 (32%). PRA was initially elevated in 41 patients, PA levels in 14, and 13 patients had raised PC levels. By the fourth day, blood pressure and biochemical measures had fallen significantly while urine volume and sodium output, low on admission, had increased significantly. On admission urinary metanephrine levels were raised in four out of the 31 patients who had them measured. The height of both the systolic and diastolic blood pressures was significantly related to the severity of the alcohol withdrawal symptoms. Of the biochemical parameters measured, PC level correlated with systolic but not diastolic pressure, and urinary volume was inversely correlated with the height of the diastolic pressure. No relationship was found between blood pressure and PRA or PA level. The pressor effect of alcohol withdrawal could be due to sympathetic nervous system overactivity, or possibly to hypercortisolaemia . The first hypothesis seems more likely.

Adult↗
PubMed1984

Effect of dopamine system activation on substantia nigra pars reticulata output neurons: variable single-unit responses in normal rats and inhibition in 6-hydroxydopamine-lesioned rats.

Previous single-unit recording studies have revealed that randomly selected pars reticulata neurons respond in a highly variable and complex fashion to intravenous administration of the dopamine agonist, apomorphine. The current studies were undertaken (1) to assess whether the variable pattern of responses of reticulata neurons to intravenous apomorphine correlates with their sites of projection and (2) to determine how reticulata responses to apomorphine might be altered by the presence of striatal dopaminergic supersensitivity. Extracellular, single-unit recording studies were conducted in anesthetized, paralyzed rats. Pars reticulata neurons were identified by antidromic activation from either the ventromedial nucleus of the thalamus or superior colliculus. Neurons of both subpopulations exhibited similar, highly variable changes in firing rate during the 10-min period immediately following intravenous injection of 320 micrograms/kg of apomorphine, a dose of the drug considered sufficient to stimulate striatal postsynaptic dopamine receptors. These responses, which were not qualitatively different from those previously observed among reticulata cells not distinguished on the basis of projection site, could be reversed by subsequent administration of dopamine antagonist drugs. In contrast to the variable responses in normal animals, the same dose of apomorphine caused a rapid and usually total inhibition of pars reticulata cell firing in rats which received 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway 6 to 8 weeks prior to recording experiments. These inhibitions of firing could also be reversed by administration of dopamine antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Dopamine modulation of the effects of gamma-aminobutyric acid on substantia nigra pars reticulata neurons.

Studies were conducted to assess whether basal ganglia output neurons originating in the substantia nigra pars reticulata might be affected by dopamine released from dendrites of neighboring substantia nigra pars compacta neurons. Dopamine applied by iontophoresis increased the baseline firing rates of approximately half of the substantia nigra pars reticulata cells tested. The more significant finding, unrelated to the increase in firing, was the ability of dopamine to attenuate the inhibitory responses of these cells to iontophoretically applied gamma-aminobutyric acid. These findings suggest a role for dopamine as a neuromodulator and further suggest that it can act at sites beyond the striatum to modify transmission from the basal ganglia to motor nuclei.

Action Potentials↗
PubMed1982

Chronic L-DOPA-pretreatment of rats: an electrophysiological and biochemical study in the basal ganglia.

Treatment of rats with L-DOPA (251.25 mg as the methyl ester HCl/kg) plus benserazide (B, 50 mg/kg) (L-DOPA+B), twice daily (i.p.) for 5 days or 12 days resulted in the dopamine (DA) neurons of the substantia nigra pars compacta becoming subsensitive to the rate-depressing effects of D-amphetamine (i.v.) 16 to 24 h after the last chronic drug dose. In contrast, pretreated rats were significantly less sensitive than control rats to the rate depressant effects of apomorphine (i.v.) after 12, but not 5 days of L-DOPA+B-pretreatment. After 5, but not 12 days of L-DOPA+B-pretreatment, a significant increase in the number of spontaneously active DA neurons was noted in the substantia nigra pars compacta. Caudate tyrosine hydroxylase was examined and a significant increase in apparent Vmax was noted after 5 days of L-DOPA+B, with no apparent change being noted in Km for cofactor. At this time, no change was noted in caudate DA or HVA concentrations. Several distinct processes may be occurring in response to the L-DOPA+B-pretreatment: (1) the DA autoreceptors located on cell bodies in the substantia nigra have become subsensitive after 12 days of L-DOPA+B-pretreatment; (2) the subsensitivity to D-amphetamine seen after both chronic schedules is probably unrelated to the subsensitive DA autoreceptors and may depend upon homeostatic alterations in neurotransmitter systems other than those utilising DA; (3) the activation of tyrosine hydroxylase may be a reflection of the increase in the number of spontaneously active units.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Effects of benzodiazepines on single unit activity in the substantia nigra pars reticulata.

Intravenous administration of two benzodiazepines, flurazepam and diazepam, had an inhibitory effect on the firing rates of neurons of the substantia nigra pars reticulata, a brain region with an identified GABAergic innervation. Diazepam was more potent than flurazepam. Bicuculline and picrotoxin, two drugs which block GABAergic transmission, and caffeine and theophylline, two methylxanthines which inhibit benzodiazepine binding, all reversed the inhibition produced by diazepam. The action of theophylline was less consistent than that of caffeine. Similarly, Ro 15-1788, an imidazodiazepine which putatively functions as a specific benzodiazepine antagonist, reversed the diazepam-induced inhibition. These findings are consistent with previous reports which suggest that the benzodiazepines may act through a GABAergic mechanism. In a separate group of experiments, caffeine or Ro 15-1788 was administered alone. While caffeine excited all reticulata, generally had little excitatory effect. These results suggest: 1) that cells of the substantia nigra pars reticulata may not receive a substantial, tonic inhibition mediated by an endogenous benzodiazepine-like substance; and 2) that the methylxanthines may increase reticulata cell firing, at least in part, through mechanisms unrelated to the blockade of benzodiazepine receptors.

Animals↗
PubMed1982

Apomorphine increases the activity of rat globus pallidus neurons.

Systemic administration of apomorphine, 0.08-1.0 mg/kg, caused a haloperidol-reversible increase in the unit activity of spontaneously firing neurons in the rat globus pallidus. Low doses of apomorphine (50, 20 micrograms/kg), which are thought to produce a net decrease in the stimulation of postsynaptic dopamine receptors, did not cause effects opposite to those observed with larger doses in 96% of the cells monitored. Blockade of dopamine receptors by administration of haloperidol did cause a moderate reduction in neuronal activity but only after administration of fairly high doses.

Animals↗
PubMed1982

Time schedule of apomorphine administration determines the degree of globus pallidus excitation.

Intravenous administration of a single 320 microgram/kg bolus dose of apomorphine significantly increased in unit activity of rat globus pallidus neurons. Significantly attenuated responses to apomorphine were observed when 320 microgram/kg apomorphine was administered i.v. in divided doses (5, 35, 280 microgram/kg) 3-5 min apart or when 320 microgram/kg apomorphine was given i.v. 8 min after a nonexcitatory 'priming' dose (20 microgram/kg i.v.) of apomorphine. These results suggest that the expression and magnitude of apomorphine-induced excitation of pallidal neurons is influenced by the time schedule of drug administration.

Animals↗
PubMed1981

A 20-year prospective study of cirrhosis.

A total of 512 people from a defined population in west Birmingham served by a district general hospital were found to have cirrhosis in the period 1959-76. The annual incidence rose from 5.6 per 100 000 to a peak of 15.3 per 100 000 in 1974. This was due to an increase in the incidence of alcoholic cirrhosis, which in the last six years accounted for two-thirds of cases. The proportion of patients with decompensated cirrhosis when first seen (65%) did not alter during the 18 years. This was reflected in a death rate of 78% among the 468 patients traced up to the end of 1978. Liver failure, hepatoma, and gastrointestinal haemorrhage accounted for almost three-quarters of the deaths. The proportion of patients who survived for five years was 36% for alcoholic cirrhosis, 14% for cryptogenic cirrhosis, and 60% for chronic active hepatitis, and these figures too remained constant throughout the 18 years. Modern methods of treatment for decompensated cirrhosis did not improve prognosis and only abstention in patients with alcoholic cirrhosis had a beneficial effect on survival. Since alcoholic cirrhosis is now the most common form of the disease it is important to recognise those at risk and to encourage abstinence; also, more efforts are needed to identify the causes of cryptogenic cirrhosis. Whatever the cause, cirrhosis needs to be diagnosed before decompensation occurs, if treatment is to have any effect.

Age Factors↗
PubMed1981

Noise and stress: a comprehensive approach.

The fundamental purposes of hearing are to alert and to warn. As a result sound directly evokes emotions and actions. The processing of sound by the brain is outlined to provide a biological and psychological basis for understanding the way in which sound can become a human stressor. The auditory orienting response, startle reflex and defensive response translate sound stimuli into action and sometimes into stress induced bodily changes through "fight or flight" neural mechanisms. The literature on the health and mental health effects of noise then is reviewed in the context of an integrated model that offers a holistic approach to noise research and public policy formulation. The thesis of this paper is that research upon, and efforts to prevent or minimize the harmful effects of noise have suffered from the lack of a full appreciation of the ways in which humans process and react to sound.

Auditory Pathways↗
PubMed1981

Neuronal responses of the globus pallidus to systemic administration of d-amphetamine: investigation of the involvement of dopamine, norepinephrine, and serotonin.

Systemic administration of d-amphetamine (d-AMP) caused significant increases in the unit activity of spontaneously firing neurons in the rat globus pallidus. Intravenous injection of 0.2 mg/kg of d-AMP produced an average increase of 32% while a cumulative dose of 6.4 mg/kg of d-AMP increased cell firing 81% above base line control. The excitatory effects of d-AMP on pallidal cells were effectively blocked and reversed by haloperidol. Increasing intravenous doses of l-amphetamine (l-AMP), totaling 12.8 mg/kg, caused a slight excitation of pallidal neurons. The average maximum increase was 18.3%. Minor rate-elevating effects were also observed after systemic administration of desmethylimipramine and clonidine. The serotonin uptake inhibitor, fluoxetine, produced varied changes in firing frequencies. Pretreatment with reserpine and alpha-methyl-p-tyrosine significantly attenuated the d-AMP-induced increase in pallidal activity. These results suggest that dopamine plays a prominent role in mediating the stimulatory effects of d-AMP on the firing rates of a population of globus pallidus cells in gallamine-paralyzed rats.

Animals↗