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Biomedical subjects

J D Lane

Publications and source records attributed to J D Lane.

At least 73 records · Page 4Linked to original sources

Caffeine and cardiovascular responses to stress.

Caffeine and psychologic stress have similar physiologic effects. Moderate doses of caffeine were found to elevate blood pressure in healthy, young males during periods of rest and stress. Blood pressure during stress was also significantly higher after caffeine had been consumed. The elevation of blood pressure due to caffeine appears to add to that elicited by stress. The implications of these results for prevention and treatment of cardiovascular disease are discussed.

Adolescent↗

Turnover rates of amino acid neurotransmitters in regions of rat cerebellum.

The turnover rates of aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, alanine, serine, and glycine were measured in five regions of rat cerebellum. Turnover rates of the putative neurotransmitters (aspartate, glutamate, and GABA) were 2-20-fold higher than those of alanine and serine, and generally consistent with the proposed neurotransmitter functions for these amino acids. However, glutamate turnover was high and similar in magnitude in the deep nuclei and granule layer, suggesting possible release, not only from parallel fibers, but from mossy fibers as well. The differential distribution of turnover rates for GABA supports its neuronal release by Purkinje, stellate, basket, and Golgi cells, whereas aspartate may be released by both climbing and mossy fibers. The distribution of glycine turnover rates is consistent with release from Golgi cells, whereas alanine may be released from granule cell parallel fibers. Turnover rates measured in two other motor areas, the striatum and motor cortex, indicated that utilization of these amino acid neurotransmitters is differentially distributed in brain motor regions. The data indicate that turnover rate measurements may be useful in identifying neurotransmitter function where content measurements alone are insufficient.

Amino Acids↗

Type A behavior and elevated physiological and neuroendocrine responses to cognitive tasks.

Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.

Behavior↗

Changes in biogenic amine and benzodiazepine receptors correlated with conditioned emotional response and its reversal by diazepam.

Groups of littermate rats were trained to respond for food reinforcement on a variable interval one-min (VI 1) schedule, after which they were classically conditioned to associate a conditioned stimulus (CS) with footshock (conditioned emotional response; conditioned suppression; CER). Two control groups received yoked footshock (no CS) or the visual-auditory stimulus only (no footshock). On test day, a group of the CER conditioned animals received injections of either vehicle or diazepam prior to exposure to the VI 1 food-reinforced schedule. After 30 min of the VI 1 schedule, the CS was presented continuously for 15 min, after which the animals were decapitated, the brains removed, membranes prepared and in vitro receptor binding evaluated. During the CS, the CER animals suppressed responding and exhibited conditioned fear (emotional) behavior, while the control groups, and animals given acute diazepam, maintained normal responding. [3H]Diazepam binding was reduced in the CER animals, yet acute benzodiazepine administration did not effect this binding. [3H]QNB binding was reduced by CER and increased by diazepam administration. Adrenergic, serotonergic and dopaminergic systems were also evaluated. Traditional biogenic amine systems may respond to CER and diazepam administration in some compensatory manner.

Animals↗

Biogenic monoamine turnover in discrete rat brain regions is correlated with conditioned emotional response and its conditioning history.

The content and turnover of dopamine, norepinephrine and 5-hydroxytryptamine (serotonin), and the content of their respective major metabolites were evaluated in 19 discrete brain areas of rats exposed to conditioned emotional response (CER), and in control groups which received either equivalent yoked shock (shock only) or compound stimulus presentation (tone only). On test day, CER animals suppressed responding and exhibited forms of emotional behavior after presentation of the conditioned stimulus (CS); while shock only and tone only control groups, and CER animals which received an acute dose of diazepam prior to testing, did not suppress. Few changes were observed in content of the biogenic amines or their metabolites, suggesting that the behavioral manipulations were acting within normal physiological limits. On the other hand, numerous changes were observed in the utilization of the 3 biogenic monoamines, which were correlated with the conditioning-anxiety (comparisons of CER vs shock only) and the shock history (comparison of shock only vs tone only). These observations are consistent with putative neural pathways in the frontal cortex, septum, nucleus accumbens, amygdala, striatum, hippocampus and brain stem (which utilize specific monoamines), and with discrete brain areas which have been implicated in classical conditioning and CER-related phenomena. These observations suggest roles for biogenic monoamines in mediating or responding to the classical conditioning and emotional components of the paradigm.

Animals↗

Amino acid neurotransmitter utilization in discrete rat brain regions is correlated with conditioned emotional response.

The content and utilization of amino acid neurotransmitters were evaluated in discrete brain areas of rats exposed to a conditioned emotional response (CER) procedure and in control groups which received either equivalent yoked shock history (shock only) or compound stimulus presentation (tone only). On test day, CER animals suppressed responding and exhibited anxious behavior after presentation of the CS, while shock only and tone only control groups, or CER animals which received an acute dose of diazepam prior to testing, did not suppress. Few changes were observed in the content of amino acids, suggesting that the behavioral manipulations were acting within normal physiological limits. On the other hand, numerous changes were observed in the utilization (turnover, metabolism) of the amino acid neurotransmitters. The effects of a history of shock presentation (shock only versus tone only) were persistent long after the conditioning sessions were terminated, and resulted in decreased turnover of the amino acids in many areas. CER conditioning-emotion (CER versus shock only) produced an increase in the turnover of aspartate and glutamate in many structures, while changes in GABA turnover were generally limited to decreases in limbic areas. If CER represents an animal model of anxiety, these observations may suggest roles for neurons which utilize amino acids in mediating or responding to emotional components of the paradigm.

Amino Acids↗

Use of a single compartment LCEC cell in the determinations of biogenic amine content and turnover.

Content and specific radioactivity of the biogenic monoamines and content of their precursors and metabolites were simultaneously determined in CNS tissue extracts with a high pressure liquid chromatography system (HPLC). The content of dopamine, norepinephrine, serotonin. 5-hydroxyindoleacetic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylethyleneglycol and the turnover rate of dopamine, norepinephrine and serotonin were measured in discrete rat brain regions using a one compartment electrochemical detector cell coupled to a C18-reverse phase HPLC column. The small fluid volume dead space of the cell allows the direct and precise collection of individual peaks for determining specific radioactivities. This method is especially suitable for central nervous system tissue samples from 8-20 mg wet weight and the sensitivity of the system in its routine configuration is approximately 2 pmol. This method for determinations of turnover is appropriate for investigations of animals in sensitive behavioral paradigms.U

Animals↗

Brain neurotransmitter turnover correlated with morphine-seeking behavior of rats.

Neurochemical substrates of intravenous opiate self-administration were investigated in rats using littermate controls for vehicle and passive morphine infusion. The rates of turnover of the putative neurotransmitters, dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, aspartate and glutamate were concurrently measured in eleven brain regions of rats intravenously self-administering morphine and yoked-morphine or yoked-vehicle infused littermates. The passive infusion of morphine resulted in significant changes in the rates of turnover of the biogenic monoamine and amino acid neurotransmitters in six brain regions with the caudate nucleus-putamen-globus pallidus showing the most changes. The contingent infusion of morphine resulted in changes in utilization rates that were generally greater in both magnitude and number than the effects of the drug itself. Twenty-nine significant changes were observed in the self-administering group with most changes occurring in limbic structures. The neurotransmitter turnover rate changes resulting from contingent administration suggest that the drug administration environment is an important factor that should be considered in studies of interactions between drugs and neuronal systems.

Amino Acids↗

Effects of cigarettes on saliva cortisol levels.

We determined the effects of cigarette deprivation and smoking on saliva cortisol levels in the presence and absence of an operant, monetarily reinforced work task. Subjects were randomly exposed to the following four experimental conditions over successive sessions: no smoking, smoking, no smoking + work, and smoking + work. Measurements of cortisol levels in saliva were determined before and after each daily session. Saliva cortisol levels declined from the beginning to the end of sessions and the end-of-session saliva cortisol levels were not affected by any of the four experimental conditions. Increased cigarette smoking in the presence of the work task also did not affect saliva cortisol levels. Our data do not support: reports of increased cortisol levels as a consequence of smoking or theories relating cortisol and endorphin release to nicotine habituation.

Adult↗

Impaired permeability of the blood-cerebrospinal fluid barrier in hyperphenylalaninaemia.

In hyperphenylalaninaemic rats the accumulation of 5-hydroxytryptophan (5-HTP) in the cerebrospinal fluid (CSF) could be shown in spite of the fact, that the 5-HTP levels of serum and brain remain constant. In vitro studies of the influx and efflux of 5-HTP and phenylalanine on isolated beef choroid plexus suggested that both aminoacids use the same carrier system. It is concluded that a high concentration of phenylalanine inhibits the re-uptake of 5-HTP by the endothelial cells of the choroid plexus. Additionally, an increased efflux of 5-HTP from choroid plexus leads to the accumulation of 5-HTP in the cerebrospinal fluid.

5-Hydroxytryptophan↗

Neurotransmitter turnover in rat striatum is correlated with morphine self-administration.

Drugs of abuse probably exert their reinforcing effects through 'reward' pathways in the central nervous system (CNS). Neuronal systems mediating opiate reinforcement have been investigated using pharmacological and electrolytic lesion procedures. Drugs that interfere with catecholaminergic and cholinergic neuronal activity decrease intravenous (i.v.) morphine self-administration in monkeys and rats. Electrolytic lesion procedures in rats have demonstrated that the medial forebrain bundle and caudate nucleus are important in maintaining i.v. morphine self-administration. We have now carried out a direct investigation of striatal (caudate nucleus, putamen and globus pallidus) neuronal systems. We show here that striatal catecholaminergic systems are important in mediating opiate reinforcement, and present direct evidence for the involvement of neurotransmitter systems in morphine reward.

Animals↗

Amantadine reduces haloperidol-induced dopamine receptor hypersensitivity in the striatum.

In this report evidence is presented that amantadine hydrochloride greatly reduced the development of dopaminergic receptor hypersensitivity in the striatum, which normally results following chronic haloperidol administration using both a stereotyped behavior bioassay and a [3H]spiroperidol receptor binding assay. Amantadine prophylaxis reduced maximal ligand binding to near control levels and also significantly reduced apomorphine induced stereotypy. These results clearly demonstrate that amantadine greatly reduced haloperidol-induced striatal dopamine receptor hypersensitivity and support the hypothesis that amantadine given concurrently with neuroleptic agents might serve to prevent the development of human tardive dyskinesia.

Amantadine↗