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J A Engel

Publications and source records attributed to J A Engel.

At least 55 records · Page 3Linked to original sources
PubMed1993

Anxiolytic-like action of centrally administered galanin.

The neuropeptide galanin is present in limbic brain areas important for emotionality. We examined whether central galanin may be involved in mechanisms of anxiety. Rats were tested in a pharmacologically validated animal model of anxiety, the Vogel punished drinking test. A 100% increase of punished responding was seen after 3 nmol galanin i.c.v. After 15 nmol, signs of sedation were seen, and no increase of punished responding could be observed. Drinking motivation, shock thresholds and exploratory locomotor activity were not affected by 3 nmol galanin. These results support a specific anxiolytic-like action of galanin, similar to that of the functionally related peptide, neuropeptide Y.

Animals↗
PubMed1993

The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine.

It has been suggested that ethanol may interact with the central nicotinic acetylcholine receptor, thus providing a basis for the often observed high consumption of both ethanol and nicotine. In the present in vivo microdialysis study, ethanol (2.5 g/kg) moderately increased dopamine overflow in the rat nucleus accumbens. The central nicotinic acetylcholine receptor antagonist mecamylamine totally counteracted this effect in a dose (1.0 mg/kg) that did not alter dopamine overflow per se. Ethanol also increased the overflow of dihydroxyphenylacetic acid and homovanillic acid, but this effect was not altered by mecamylamine (1.0 mg/kg). Furthermore, the ethanol-induced enhancement of 3,4-dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted no effects per se. Neither ethanol nor mecamylamine changed the catecholamine synthesis rate in the striatum or the cerebral cortex. These results provide further evidence that ethanol-induced activation of the mesolimbic dopamine system (increased dopamine synthesis and release) may be mediated via stimulation of central nicotinic acetylcholine receptors. It is suggested that antagonists of central nicotinic acetylcholine receptors may be useful in the treatment of alcoholism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

C-fos antisense in the nucleus accumbens blocks the locomotor stimulant action of cocaine.

Systemic cocaine induces c-fos expression in rat striatum. The functional role of this phenomenon remains unknown. Recently, selective inhibition of gene expression in the brain using antisense oligodeoxynucleotides became possible. Here, we report that bilateral administration of an antisense oligo against c-fos in the nucleus accumbens blocks cocaine induced locomotor stimulation, without affecting spontaneous exploratory activity. A control sense oligo was inactive. This finding suggests a role for c-fos in mediating psychostimulant effects of cocaine.

Animals↗
PubMed1993

Effect of ageing on extracellular ascorbate concentration in rat brain.

In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of ageing on extracellular ascorbate (AA) concentration in the rat brain. Recordings from the nucleus accumbens in 3-, 6- and 18-month-old Sprague-Dawley rats revealed an age-related decrease in basal extracellular AA concentration. The mean AA current measured in 18-month-old rats was less than 10% of the current measured in 3-month-old rats. Systemic administration of ethanol (1.0 g/kg, i.p.) caused an increase in the AA signal measured in this area in all 3 age groups tested. However, the effect on AA was significantly less pronounced in 18-month-old rats. Further analysis of the AA signal revealed a gradual increase in AA release during terminal anoxia. Also in this case the effect on AA was significantly less pronounced in 18-month-old rats. This difference was also observed in the caudate putamen, another dopamine (DA) rich area in the brain. No significant difference in AA release was observed in the frontal cortex where the DA concentration is low. The increase in AA was followed by a pronounced increase in extracellular DA in the nucleus accumbens and caudate putamen. This release of DA was accompanied by a prompt reversal of the AA signal possibly explained by a DA-dependent autoxidation of AA. These results suggest a role for brain AA in the process of ageing.

Aging↗
PubMed1992

Rapid changes in ascorbate and dopamine release in rat nucleus accumbens after intracerebroventricular administration of NMDA.

In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of intracerebroventricular (i.c.v.) administration of N-methyl-D-aspartic acid (NMDA) on neuronal activity in rat nucleus accumbens. Infusion of a low dose of NMDA (1 nmol) was followed a few minutes later by rapid changes in both Peak 1 and Peak 2 heights indicating large but short-lived increases in the extracellular concentrations of ascorbate and catecholamines, respectively. These responses did not seem to be dependent on the dose infused since infusion of NMDA for a longer time period neither changed the amplitude nor the time-course of these effects. The increase in Peak 2 height was resistant to pargyline pretreatment indicating that this response mainly reflected the release of dopamine. The administration of NMDA was followed by behavioural activation in the animals but not convulsions. Co-administration of the competitive NMDA receptor antagonist, CPP (1 nmol), completely blocked these effects while the acetylcholine receptor antagonist, atropine (1.5 nmol), and the GABA receptor antagonist, picrotoxin (1 nmol), failed in this respect. The phenomenon spreading depression is discussed as a possible explanation of these results.

Animals↗
PubMed1992

The 5,7-DHT-induced anticonflict effect is dependent on intact adrenocortical function.

We have recently reported that the anxiolytic-like effect observed in rats severely depleted of brain serotonin (5-HT) by means of 5,7-DHT is indirect and probably involves the GABA(A)/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC). One tentative explanation for this effect considered the involvement of corticosteroids. In the present series of experiments we have therefore investigated the effect of adrenalectomy (ADX) on the 5,7-DHT-induced anxiolytic-like effect displayed by rats in Vogel's conflict test. ADX totally abolished the anticonflict effect of the 5,7-DHT lesion. Replacement treatment with corticosterone, but not with dexamethasone, reinstated the anticonflict effect. These results indicate that an intact adrenocortical function, possibly via brain steroid type I receptors, is required for the expression of the 5,7-DHT-induced anxiolytic-like effect. It is postulated that ADX lowers the concentration of endogenous positive modulators at the GABAA/BDZ-RC to a level no longer sufficient to produce anxiolytic-like effects in 5,7-DHT-lesioned animals. The finding that 5,7-DHT-lesioned animals were more sensitive than sham-lesioned controls to the anticonflict effect of the barbiturate-like corticosteroid THDOC provides further support for the contention that an increased endogenous activity at the GABAA/BDZ-RCes is involved in the anxiolytic-like effect observed in rats with a severe depletion of brain 5-HT.

5,7-Dihydroxytryptamine↗
PubMed1992

Intracerebroventricular 5,7-DHT alters the in vitro function of rat cortical GABAA/benzodiazepine chloride ionophore receptor complexes.

We have earlier presented data indicating that the anxiolytic-like effect obtained in rats after depletion of brain 5-HT by means of PCPA or 5,7-DHT treatment is indirect and appears to involve the GABAA/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC), and that it is abolished by adrenalectomy. In the present series of experiments we have therefore investigated the 36Cl(-)-uptake in rat synaptoneurosomal preparations of central cortices from 5,7-DHT- and SHAM-lesioned animals. The GABA as well as the 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (THDOC) induced picrotoxin-sensitive increase in 36Cl(-)-uptake was significantly lower than that observed in the SHAM-lesioned animals, indicating that the 5,7-DHT lesion has rendered the GABAA/BDZ-RC subsensitive to two of its tentative endogenous ligands. This effect of the 5,7-DHT lesion on the function on the GABAA/BDZ-RC was reversed by adrenalectomy, indicating that an intact adrenocortical function is required for the development of GABAA/BDZ-RC subsensitivity in 5,7-DHT-lesioned rats. A tentative conclusion of these findings is that the 5,7-DHT lesion induces an increase in release of GABA and/or barbiturate-like steroids and that this increase is reversed by adrenalectomy. The findings from these in vitro studies parallel those from our previous behavioral experiments and provide further support for the notion that a decreased serotonergic influence in the central nervous system may, possibly via the adrenocortical system, enhance the function of the GABAA/BDZ-RC.

5,7-Dihydroxytryptamine↗
PubMed1992

Ethanol-induced locomotor activity: involvement of central nicotinic acetylcholine receptors?

Ethanol and nicotine have many psychopharmacological effects in common, which could explain why coadministration of these compounds often is observed in individuals. In the present study in mice, low doses of nicotine in a complex manner altered the locomotor activity (LMA) stimulatory effect of different doses of ethanol, whereas the quaternary nicotine analog tetramethylammonium did not. The blood-brain-barrier-penetrating nicotine antagonist mecamylamine (2.0 and 4.0 mg/kg), but not the quaternary nicotine antagonist hexamethonium (4.0 and 8.0 mg/kg), partly counteracted the LMA stimulatory effect of ethanol (3.0 g/kg) in doses having no LMA reducing effects per se. Furthermore, the dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) quotient increase in mouse brain after ethanol 3.0 g/kg was partly antagonized by mecamylamine 2.0 and 4.0 mg/kg. These results suggest that part of the LMA and DA turnover-increasing effect of ethanol is mediated via activation of central nicotinic acetylcholine receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

The clinical problem of occult cardiac amyloidosis. Forensic implications.

A 68-year-old man with known coronary heart disease experienced rapidly progressive cardiac dysfunction and was found to have occult cardiac amyloidosis at autopsy. The amyloidosis was undiagnosed during life and initially at autopsy. Marked diffuse involvement of the intramural coronary arteries by amyloid deposits resulted in severe luminal compromise of numerous medium and small vessels. The myocardium proper was virtually spared from amyloid deposits. Amyloid-related coronary narrowing contributed to cardiac ischemia and sudden death. The significance of amyloid coronary disease in this patient relates primarily to the difficulty in considering the diagnosis when other reasons for cardiac signs and symptoms preexist. Also, the adverse effects of amyloid coronary disease may be profound without direct myocardial involvement.

Aged↗
PubMed1992

Progress in blood lipid reporting practices by clinical laboratories in North America. Changes from 1985 to 1990.

In an attempt to assess the impact of the National Cholesterol Education Program recommendations and to provide follow-up to a 1985 survey of blood lipid reporting practices in 152 academic clinical laboratories in North America, the same laboratories were resurveyed regarding current blood lipid-reporting practices. All 97 laboratories that responded to our survey routinely measured serum total cholesterol, while 94% measured high-density lipoprotein cholesterol, 99% measured triglycerides, 26% apolipoproteins A1 and B, and a single laboratory measured apolipoprotein E. There was a marked downward shift in reference ranges for serum total cholesterol used by laboratories in 1990 compared with 1985. Of the laboratories responding to both surveys, 90% lowered their reported reference values. Changes in the sources of reference ranges were also noted. The percent of laboratories using reference ranges based on age and sex fell from 52% to 21% and from 31% to 10%, respectively. The number of laboratories designating patient risk for coronary heart disease rose from 31% to 72%. Currently, 61% of laboratories designating risk use the National Cholesterol Education Program guidelines for serum total cholesterol. The use of other risk designations, including high-density lipoprotein--cholesterol, total cholesterol to high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, and apolipoproteins changed only modestly during the 5-year interval. The current reporting patterns reflect simplified and more uniform practices apparently in response to the National Cholesterol Education Program.

Adult↗
PubMed1991

Evidence for a role for dopamine in the diazepam locomotor stimulating effect.

It is well known that benzodiazepines produce dependence in humans and locomotor stimulation in experimental animals. In this study the possible involvement of catecholamines in the diazepam-induced locomotor stimulation in mice were investigated. Diazepam was found to have a biphasic effect; increasing locomotor activity at a low dose (0.25 mg/kg), while decreasing it at higher doses (greater than 0.5 mg/kg). The locomotor stimulating effect of diazepam was effectively blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil, as well as with the catecholamine synthesis inhibitor alpha-methyltryrosine and the dopamine receptor antagonists haloperidol, spiperone and SCH 23390. Taken together, these data indicate that the locomotor stimulating effect observed after low doses of diazepam is due to activation of brain dopaminergic systems involved in locomotor activity. The observations are discussed in relation to the hypothesis that dependence-producing drugs activate specific brain reward systems.

Animals↗
PubMed1991

Involvement of the GABAA/benzodiazepine chloride ionophore receptor complex in the 5,7-DHT Induced anticonflict effect.

The effects of drugs interacting with the GABAA/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC) on the anticonflict and biochemical effects observed after intracerebroventricular (i.c.v.) administration of 5,7-dihydroxytryptamine (5,7-DHT; 450 micrograms -14 days) were investigated in the rat using a modified Vogel's drinking conflict test. The GABAergic antagonistic drugs bicuculline, picrotoxin and Ro 15-4513 all counteracted the 5,7-DHT induced anxiolytic-like action in doses that did not alter the behavior per se, whereas flumazenil was ineffective in this respect. Also i.c.v. administration of 5-HT antagonized the 5,7-DHT induced anticonflict effect. Furthermore, 5,7-DHT-lesioned animals appeared more sensitive to the anticonflict effects of diazepam than sham-lesioned controls. The 5,7-DHT treatment produced marked depletions of 5-HT in the limbic system (80-90%) and hippocampus (90-95%), and an increase in the 5-HIAA/5-HT quotient in hippocampus. The effects on the levels of noradrenaline were comparatively small. The doses of bicuculline and picrotoxin antagonizing the 5,7-DHT induced anticonflict effect did not uniformly influence 5-HT levels or 5-HIAA/5-HT quotients. It is suggested that the anxiolytic-like effect observed in 5,7-DHT-lesioned rats in Vogel's drinking conflict test involves enhanced transmission at the GABAA/BDZ-RC.

5,7-Dihydroxytryptamine↗
PubMed1990

Alpha 1- and beta-adrenoceptor stimulation potentiate the anticonflict effect of a benzodiazepine.

Interactions between different noradrenaline (NA)-active drugs and the benzodiazepine alprazolam (APZ) were examined in a modified Vogel's drinking conflict test in the rat. In a dose (0.5 mg/kg) which did not alter the behavior by itself, the alpha 2-adrenoceptor antagonist yohimbine consistently was found to enhance the anticonflict effect of APZ (0.5 mg/kg). The yohimbine induced potentiation of the APZ effect was counteracted both by the selective alpha 1-adrenoceptor antagonist prazosin (0.25 mg/kg) and the beta-adrenoceptor antagonist propranolol (2.0 mg/kg), but not by the selective beta 1-adrenoceptor antagonist metoprolol (2.0 mg/kg). Similar potentiating phenomena were obtained after co-administration of APZ (0.5 mg/kg) with the selective alpha 1-adrenoceptor agonist ST 587 (0.5-1.0 mg/kg) as well as with the suggested beta 2-adrenoceptor agonist clenbuterol (1.0 mg/kg). The results indicate that the potentiative effects of alpha 2-adrenoceptor antagonists on BDZ induced anticonflict action may be due to increased stimulation of alpha 1- and beta-adrenoceptors, via enhanced NA release. The findings are discussed in relation to the signal-to-noise hypothesis of NA function, and in relation to the suggested NA involvement in anxiety-related behavior.

Alprazolam↗
PubMed1990

Environment-dependent effects of ethanol on DOPAC and HVA in various brain regions of ethanol-tolerant rats.

The development of tolerance to the behavioral and biochemical effects of ethanol was studied. Rats were made tolerant to ethanol by the administration of daily ethanol injections (3 g/kg, IP) for 7 and 28 days. Tolerance developed both to the behavioral (hypothermic, sedative) and biochemical (accumulation of dopamine metabolites in various brain areas) actions of ethanol. However, it was found that this tolerance to both the behavioral and biochemical effects of ethanol was no longer present when previously ethanol-tolerant animals were moved from their home environment and given a challenge dose of ethanol (2.5 g/kg; IP) in a new, unfamiliar environment. Our findings confirm that ethanol tolerance cannot be explained on the basis of a singular neurochemical event. The development of ethanol tolerance is due to a complex interaction between environmental, learning, and biochemical factors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Serotonergic involvement in conflict behaviour.

The effects of different manipulations of brain serotonergic (5-HT) systems were investigated in Montgomery's conflict test, an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. The putative 5-HT1A receptor agonists buspirone, gepirone, ipsapirone and 8-OH-DPAT all produced anxiolytic-like effects in narrow low dose-ranges, while in higher doses the behavior returned towards that seen in controls and, after the highest doses of buspirone and gepirone, was suppressed below that of controls. The 5-HT precursor L-5-HTP produced a biphasic dose-response curve. In a single low dose an anxiolytic-like action was obtained, while in the highest dose a clear-cut anxiogenic-like action was observed. The 5-HT depleting agents parachlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine (5,7-DHT) both produced anxiolytic-like effects. Thus, anxiolytic-like and anxiogenic-like effects after various manipulations of brain 5-HT neurotransmission can be obtained also in an animal anxiety model involving neither consummatory behavior nor punishment. The anxiolytic-like effects after all these treatments are suggested to be due to decreased brain 5-HT neurotransmission, while the anxiogenic-like effect obtained after the highest dose of L-5-HTP is suggested to derive from increased 5-HT neurotransmission. Furthermore, using a modified Vogel's conflict model it was investigated whether the anxiolytic-like effects obtained after PCPA and 5,7-DHT involve the GABAA/benzodiazepine (BDZ) chloride ionophore receptor complex. Both the BDZ receptor antagonist flumazenil and the GABAA receptor antagonist bicuculline counteracted the PCPA induced anticonflict effect in doses which did not affect the behavior per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of amperozide on the synthesis and turnover of monoamines in rat brain.

The effects of amperozide on the synthesis and the turnover of monoamines in different brain regions of the rat were determined using both ex vivo and in vivo biochemical techniques (i.e. post-mortem measurements of the tissue levels by HPLC-EC, and direct measurements with the in vivo voltammetry technique). It was found that amperozide slightly increased the DOPA accumulation and the DOPAC content in limbic brain areas but not in the striatum. The DOPA accumulation was also slightly increased in the noradrenaline rich cortical region indicating increased synthesis of noradrenaline. Furthermore, amperozide increased the utilization of noradrenaline after tyrosine hydroxylase inhibition by alpha-methyl-p-tyrosine. The synthesis of 5-HT was not significantly altered by amperozide. In conclusion, the biochemical data obtained in this study suggest that amperozide produces preferential effects on the mesolimbic dopaminergic system. In addition, amperozide also interacts with the noradrenergic system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Progress in lipid reporting practices and reliability of blood cholesterol measurement in clinical laboratories in Nebraska. Efforts to align results with the Centers for Disease Control, and feasibility of meeting National Cholesterol Education Program Guidelines.

The National Cholesterol Education Program has recommended that all laboratories be consistent, precise, and accurate in the reporting and measurement of blood cholesterol levels. In a follow-up to a 1984 survey study, we assessed the changes in reporting procedures for measurements of blood lipid levels in 16 clinical laboratories in Nebraska. Using human serum reference materials of known cholesterol concentrations provided by the Centers for Disease Control, we also assessed the precision and accuracy of measurement of blood cholesterol levels in clinical laboratories in Nebraska. Fourteen of the 16 laboratories restudied in 1987 had altered the reference range for total serum cholesterol since 1984, 86% of whom lowered the upper limit of the reference range. Eleven of 16 laboratories expressed reference ranges for total serum cholesterol in terms of patient age in 1987, while only 7 of 20 did in 1984. Gender-based reference ranges increased from 0 to 5 from 1984 to 1987. Similar trends were seen in the reporting of high-density lipoprotein cholesterol and triglyceride concentrations. Reporting procedures varied greatly; only 1 laboratory used National Cholesterol Education Program risk levels for measuring total serum cholesterol levels. Fifteen laboratories met the National Cholesterol Education Program recommendation for precision (coefficient of variation, less than or equal to 5%) and 78% of laboratories obtained results that satisfied the current recommendation for accuracy (within 5% of "true value," as determined by the Centers for Disease Control).

Adult↗