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Biomedical subjects

L Cook

Publications and source records attributed to L Cook.

At least 163 records · Page 9Linked to original sources
PubMed1980

Mechanism of action of the benzodiazepines: behavioral aspect.

The mechanism of action of benzodiazepines is considered from a behavioral pharmacology perspective, particularly with respect to methods that involve suppression of responding, such as the punishment-conflict model. Four biochemical hypotheses of current interrest are reviewed. 1) Several lines of evidence suggest that the benzodiazepine receptor in brain is related to the antianxiety actions of benzodiazepines, including a high correlation between potency in the binding assay and potency in the test, and some novel nonbenzodiazepine compounds that bind to the receptor and are also active in the conflict tests. 2) The evidence is mixed concerning whether inosine or hypoxanthine may be endogenous ligands for the benzodiazepine receptor. Unlike benzodiazepines, neither inosine nor hypoxanthine antagonizes convulsions induced by pentylenetetraxol in the rat. 3) Much research indicates that gamma-aminobutyric acid (GABA) mediates various electrophysiological and biochemical actions of benzodiazepines. Several studies have also found that picrotoxin or bicuculline block the behavior effects of benzodiazepines, although some conflicting results have been reported. Most available findings suggest that GABA agonists, e.g., muscimol, do not exhibit the antianxiety profile of the benzodiazepines. 4) Additional evidence has accumulated to support the hypothesis that the behavioral actions of the benzodiazepines are mediated by serotonin, possibly with the involvement of GABA.

Animals↗
PubMed1979

Effect of sex on the strain differences in hepatic metabolism of starved and nonstarved rats.

The hepatic metabolism of starved and nonstarved male and female rats from the Wistar and BHE (line 4) strains has been studied. Liver tissue was frozen between precooled copper plates and the levels of various metabolites of the glycolytic and citric acid cycle and adenine nucleotides determined. While the major differences in hepatic metabolism were attributable to the strain of animal, sex effects were also observed. These results suggest that differences in compartmental phosphorylation states may be indicative of a greater lipogenic capacity of these rats compared to normal rats.

Animals↗
PubMed1978

The r.b.e. of different-energy neutrons as determined by human bone-marrow cell-culture techniques.

The effect of X-rays and different-energy neutrons on human bone-marrow cells was studied using two different cell-culture techniques--diffusion chamber (DC) growth and colony formation in vitro (CFU-C). Based on the survival of proliferative granulocytes in DC on day 13, the D0 value was 80 rad with X-rays, and 117 rad as measured by the CFU-C assay. The D0 values for neutrons depended on the radiation source and the energy level. The r.b.e. values, which dropped with increasing energy levels of mono-energetic neutrons, were (i) 0.44 MeV; DC 3.7, CFU-C 4.1; (ii) 6 MeV; DC 1.8, CFU-C 2.0; (iii) 15 MeV; DC 1.6, CFU-C 1.6; (iv) fission neutrons; DC 2.6, CFU-C 2.4.

Bone Marrow↗
PubMed1978

Conflict behavior in the squirrel monkey: effects of chlordiazepoxide, diazepam and N-desmethyldiazepam.

Dose-response profiles were determined for chlordiazepoxide, diazepam and N-desmethyldiazepam in a squirrel monkey punishment (conflict) procedure. The monkeys were trained to lever press under a food-maintained concurrent schedule consisting of an unpunished 6-minute variable interval (VI) schedule, and a 1.5-minute VI schedule, on which responses were punished intermittently (24 response variable ratio) with electric footshocks. The three benzodiazepines effectively increased responding that had been suppressed by punishment; they had inverted U-shaped dose-effect curves. The minimum effective doses for increasing punished responding were: diazepam less than or equal to 0.31 mg/kg p.o.; N-desmethyldiazepam = chlordiazepoxide = 0.62 mg/kg. As a model to assess potential antianxiety activity, this procedure possessed excellent sensitivity and reliability. The following observations were also made. 1) During initial training, as shock intensity was increased and punished responding became suppressed, some monkeys exhibited an increase in unpunished response rates. This may have represented "positive behavioral contrast," but response rate changes were associated with changes in the amount of time the monkeys allocated to each schedule. 2) At certain dose levels, all three compounds exerted antipunishment effects 24 hours after administration. 3) As was reported previously for rats, when the monkeys had no previous drug experience ("drug-naive") they were more sensitive to the depressant effects of the benzodiazepines. With repeated administration, there was a reduction in this sedation and a concomitant increase in the antipunishment effect. This phenomenon was dose- and animal-dependent.

Animals↗
PubMed1976

Oral cholestyramine and paregoric therapy for intractable diarrhea following surgical correction of catastrophic disease of the GI tract in neonates.

Ten surgical neonates with postoperative intractable diarrhea and secondary weight loss were treated with combination cholestyramine and paregoric therapy. Within 3-5 days all infants except two showed significant clinical improvement with a decreasing number of stools, an increase in the consistency of the stool, and gradual weight gain. The exact mechanism of action of cholestyramine is not clear. It may act by binding with bile salts and/or endotoxins in the bowel lumen or decreasing the motility of the bowel. Used in combination with paregoric, a known bowel motility depressant, the doses of each medication can be kept quite low thus avoiding undesirable side effects. Medium chain triglyceride formula is helpful in some of these infants to improve fat absorption further. Medication in all of these infants has been discontinued without any adverse effects.

Administration, Oral↗
PubMed1975

Reinforcement schedules and extrapolations to humans from animals in behavioral pharmacology.

Behavior controlled by various schedules of reinforcement is useful for characterizing drugs as well as for analyzing the mechanisms of action of their effects on behavior. Conditioned avoidance techniques have been useful for studying neuroleptics and for predicting their clinical antipsychotic acitivity; the possible involvement of dopaminergic mechanisms in the effect of neurolpetics on avoidance behavior is discussed. Tricyclic antidepressant agents have been studied in assays involving interactions with other agents, such as cocaine, amphetamine and tetrabenazine. One type of operant behavior, Sidman avoidance, has been used as particularly sensitive assay for such drug interactions. Another schedule, in which "observing" responses in pigeons are measured. seems to provide a method for studying antidepressants without involving drug interaction phenomena. For tricyclic compounds, facilitation of observing responses and weak potency of conditioned avoidance inhibition constitute a pharmacological profile that seems to have some predictive value for clinical imipramine-like antidepressant activity. "Conflict (punishment) schedules have been useful for predicting antianxiety activity in man. Although the degree of anticonflict effect observed is consistent with Dew's rate dependency hypothesis, this principle does not fully account for the observed drug effects. In the conflict model, the actions of benzodiazepines differ in drug-naive versus drug-experienced animals. Experiments with parachlorophenylalnine have not yet provided clear support for the postulated role of serotonin in related phenomena.

Animals↗
PubMed1975

Behavioral analysis of the effects and mechanisms of action of benzodiazepines.

Conflict behavior is a powerful tool to reveal relevant pharmacologic correlates of the therapeutically desirable properties of benzodiazepine antianxiety compounds. The predictability of its clinical effectiveness in psychoneuroses is very high, and important quantitative and qualitative differences between compounds in this chemical class can be shown using such a behavioral technique. It is important to take these differences into account when studying biochemical correlates or mechanisms of action within the benzodiazepine class. Conflict behavior has been used to evaluate several biochemical hypotheses concerning the mechanism of action for the antianxiety properties of benzodiazepines. These studies found that inhibition of cyclic AMP phosphodiesterase did not seem to be a relevant factor. Similarly, experiments with AOAA did not provide evidence to support the involvement of GABA with benzodiazepines' antianxiety properties, nor did glycine receptor affinities correlate significantly with anticonflict effects. Thus, while it is reasonable at present to associate either GABA or glycine with the muscle-relaxant or anticonvulsant properties of benzodiazepines, no support was provided in the conflict procedure for their involvement in the anxiolytic effects. Partial support was provided for the proposal that serotonin is involved in the benzodiazepines' anxiolytic activity. This was determined in studies with the serotonin antagonists cinanserin and methysergide, which had anti-conflict activity, as well as in studies of monoamine turnover after initial chlordiazepoxide treatments to previously undrugged, conflict-trained rats.

Aminooxyacetic Acid↗