scholarly journals The role of liver tryptophan pyrrolase in the opposite effects of chronic administration and subsequent withdrawal of drugs of dependence on rat brain tryptophan metabolism

1981 ◽  
Vol 196 (1) ◽  
pp. 161-170 ◽  
Author(s):  
A A Badawy ◽  
N F Punjani ◽  
M Evans
Keyword(s):  
Chronic Administration ◽  
Tryptophan Metabolism ◽  
Chronic Morphine ◽  
Drug Induced ◽  
Tryptophan Pyrrolase ◽  
Subsequent Withdrawal ◽  
Induced Changes ◽  
Phenazine Methosulphate ◽  
The Brain

1. Chronic administration of morphine, nicotine or phenobarbitone has previously been shown to inhibit rat liver tryptophan pyrrolase activity by increasing hepatic [NADPH], whereas subsequent withdrawal enhances pyrrolase activity by a hormonal-type mechanism. 2. It is now shown that this enhancement is associated with an increase in the concentration of serum corticosterone. 3. Chronic administration of the above drugs enhances, whereas subsequent withdrawal inhibits, brain 5-hydroxytryptamine synthesis. Under both conditions, tryptophan availability to the brain is altered in the appropriate direction. 4. The chronic drug-induced enhancement of brain tryptophan metabolism is reversed by phenazine methosulphate, whereas the withdrawal-induced inhibition is prevented by nicotinamide. 5. The chronic morphine-induced changes in liver [NADPH], pyrrolase activity, tryptophan availability to the brain and brain 5-hydroxytryptamine synthesis are all reversed by the opiate antagonist naloxone. 6. It is suggested that the opposite effects on brain tryptophan metabolism of chronic administration and subsequent withdrawal of the above drugs of dependence are mediated by the changes in liver tryptophan pyrrolase activity. 6. Similar conclusions based on similar findings have previously been made in relation to chronic administration and subsequent withdrawal of ethanol. These findings with all four drugs are briefly discussed in relation to previous work and the mechanism(s) of drug dependence.

scholarly journals Enhancement of rat brain tryptophan metabolism by chronic ethanol administration and possible involvement of decreased liver tryptophan pyrrolase activity

1979 ◽  
Vol 178 (3) ◽  
pp. 575-580 ◽  
Author(s):  
A A Badawy ◽  
N F Punjani ◽  
M Evans
Keyword(s):  
Methylene Blue ◽  
Rat Brain ◽  
Chronic Ethanol ◽  
Tryptophan Metabolism ◽  
Ethanol Administration ◽  
Chronic Ethanol Administration ◽  
Tryptophan Pyrrolase ◽  
Tryptophan Concentration ◽  
Phenazine Methosulphate ◽  
The Brain

1. Chronic ethanol administration enhances rat brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain. This increased availability is not insulin-mediated or lipolysis-dependent. 2. Under these conditions, tryptophan accumulates in the liver and apo-(tryptophan pyrrolase) activity is completely abolished, but could be restored by administration of regenerators of liver NAD+ and/or NADP+. 3. All four regenerators used (fructose, Methylene Blue, phenazine methosulphate and sodium pyruvate) prevented the ethanol-induced increase in liver tryptophan concentration and the increased availability of tryptophan to the brain. 4. It is suggested that the enhancement of brain tryptophan metabolism by chronic ethanol administration is caused by the decreased hepatic tryptophan pyrrolase activity. The results are briefly discussed in relation to previous work with ethanol. 5. Fructose enhances the conversion of tryptophan into 5-hydroxyindol-3-ylacetic acid in brains of ethanol-treated rats, whereas Methylene Blue inhibits this conversion in both control and ethanol-treated animals.

scholarly journals The regulation of rat liver tryptophan pyrrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Experiments with glucose and nicotinamide

1976 ◽  
Vol 156 (2) ◽  
pp. 381-390 ◽  
Author(s):  
A A B Badawy ◽  
M Evans
Keyword(s):  
Drinking Water ◽  
Rat Liver ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Chronic Administration ◽  
Glucose Effect ◽  
Tryptophan Pyrrolase ◽  
Subsequent Withdrawal ◽  
Phenazine Methosulphate

1. Chronic administration of glucose or nicotinamide in drinking water inhibits the activity of rat liver tryptophan pyrrolase, and subsequent withdrawal causes an enhancement. The enzyme activity is also inhibited by administration in drinking water of sucrose, but not fructose, which is capable of preventing the glucose effect. 2. The inhibition by glucose or nictinamide is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. 3. The inhibition by nicotinamide is reversed by regeneration of liver NAD+ and NADP+ in vivo by administration of fructose, pyruvate or phenazine methosulphate. Inhibition by glucose is also reversed by the above agents and by NH4Cl. Reversal of inhibition by glucose or nicotinamide is also achieved in vitro by addition of NAD+ or NADP+. 4. Glucose or nicotinamide increases liver [NADPH]. [NADP+] is also increased by nicotinamide. [NADPH] is also increased by sucrose, but not by fructose, which prevents the glucose effect. Phenazine methosulphate prevents the increase in [NADPH] caused by both glucose and nicotinamide. 5. It is suggested that the inhibition of tryptophan pyrrolase activity by glucose or nicotinamide is mediated by both NADPH and NADH.

Do Benzodiazepines Interfere with the Action of Electroconvulsive Therapy?

1992 ◽  
Vol 160 (4) ◽  
pp. 545-546 ◽  
Author(s):  
Samuel I. Cohen ◽  
Claire Lawton
Keyword(s):  
British Journal ◽  
Electroconvulsive Therapy ◽  
Chronic Administration ◽  
Depressed Woman ◽  
Induced Changes ◽  
The Brain

A 67-year-old anxious and depressed woman was withdrawn from a long-term course of a benzodiazepine and soon after was given ECT. This proved ineffective, but ECT given some months later was successful. It is suggested that the chronic administration of the benzodiazepine may have induced changes in the brain that interfered with ECT.British Journal of Psychiatry (1992), 160, 545–546

Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially

2001 ◽  
Vol 280 (4) ◽  
pp. R1190-R1196 ◽  
Author(s):  
B. Bishop ◽  
G. Silva ◽  
J. Krasney ◽  
H. Nakano ◽  
A. Roberts ◽  
...  
Keyword(s):  
Body Temperature ◽  
Ambient Temperature ◽  
Induced Responses ◽  
Brain Pathology ◽  
Level Of Activity ◽  
Time Courses ◽  
Induced Changes ◽  
Subsequent Rise ◽  
The Brain

When rats, acclimated to an ambient temperature (Ta) of 29°C, are exposed to 10% O2 for 63 h, the circadian rhythms of body temperature (Tb) and level of activity (La) are abolished, Tb falls to a hypothermic nadir followed by a climb to a hyperthermic peak, Laremains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378–R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of Ta in these hypoxic-induced responses, Tb and La data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O2 from rats acclimated to 25 or 21°C. Magnitudes and rates of decline in Tb after onset of hypoxia were inversely proportional to Ta, whereas magnitudes and rates of Tb climb after the hypothermic nadir were directly proportional to Ta. No hyperthermia, so prominent at 29°C, occurred at 25 or 21°C. The hypoxic depression of La was least at 21°C and persisted throughout the hypoxia. In contrast, Ta was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in Tb. We propose that the absence of hyperthermia at 21 and 25°C as well as a persisting hypothermia may protect the brain from overt pathology.

scholarly journals Evidence that microtubules do not mediate opsin vesicle transport in photoreceptors.

1989 ◽  
Vol 109 (6) ◽  
pp. 3053-3062 ◽  
Author(s):  
D K Vaughan ◽  
S K Fisher ◽  
S A Bernstein ◽  
I L Hale ◽  
K A Linberg ◽  
...  
Keyword(s):  
Outer Segment ◽  
Lucifer Yellow ◽  
Lateral Displacement ◽  
Linear Increase ◽  
Rod Photoreceptor ◽  
Drug Induced ◽  
Membrane Assembly ◽  
Induced Changes ◽  
Vectorial Transport

The organization of the rod photoreceptor cytoskeleton suggests that microtubules (MTs) and F actin are important in outer segment (OS) membrane renewal. We studied the role of the cytoskeleton in this process by first quantifying OS membrane assembly in rods from explanted Xenopus eyecups with a video assay for disc morphogenesis and then determining if the rate of assembly was reduced after drug disassembly of either MTs or F actin. Membrane assembly was quantified by continuously labeling newly forming rod OS membranes with Lucifer Yellow VS (LY) and following the tagged membranes' distal displacement along the OS. LY band displacement displayed a linear increase over 16 h in culture. These cells possessed a longitudinally oriented network of ellipsoid MTs between the sites of OS protein synthesis and OS membrane assembly. Incubation of eyecups in nocodazole, colchicine, vinblastine, or podophyllotoxin disassembled the ellipsoid MTs. Despite their absence, photoreceptors maintained a normal rate of OS assembly. In contrast, photoreceptors displayed a reduced distal displacement of LY-labeled membranes in eyecups treated with cytochalasin D, showing that our technique can detect drug-induced changes in basal rod outer segment assembly. The reduction noted in the cytochalasin-treated cells was due to the abnormal lateral displacement of newly added OS disc membranes that occurs with this drug (Williams, D. S., K. A. Linberg, D. K. Vaughan, R. N. Fariss, and S. K. Fisher. 1988. J. Comp. Neurol. 272:161-176). Together, our results indicate that the vectorial transport of OS membrane constituents through the ellipsoid and their assembly into OS disc membranes are not dependent on elliposid MT integrity.

scholarly journals Caught in the Net: Perineuronal Nets and Addiction

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Megan Slaker ◽  
Jordan M. Blacktop ◽  
Barbara A. Sorg
Keyword(s):  
Extracellular Matrix ◽  
Drugs Of Abuse ◽  
Perineuronal Nets ◽  
Drug Induced ◽  
Brain Circuitry ◽  
Induced Changes ◽  
The Brain

Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM). Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs). This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction.

scholarly journals Effects of the haem precursor 5-aminolaevulinate on tryptophan metabolism and disposition in the rat

1987 ◽  
Vol 248 (1) ◽  
pp. 293-295 ◽  
Author(s):  
A A B Badawy ◽  
C J Morgan ◽  
N R Davis
Keyword(s):  
Mood Disorders ◽  
Tryptophan Metabolism ◽  
Tryptophan Pyrrolase ◽  
The Brain

5-Aminolaevulinate administration to rats inhibits cerebral 5-hydroxytryptamine synthesis by decreasing tryptophan availability to the brain secondarily to activation of hepatic tryptophan pyrrolase. The results show that tryptophan metabolism and disposition can be influenced by changes in liver haem concentration, and are discussed briefly in relation to mood disorders in the hepatic porphyrias.

scholarly journals Pathophysiological mechanisms underlying antipsychotic-induced tardive dyskinesia

2020 ◽  
Vol 18 (4) ◽  
pp. 169-184
Author(s):  
E. E. Vayman ◽  
N. A. Shnayder ◽  
N. G. Neznanov ◽  
R. F. Nasyrova
Keyword(s):  
Tardive Dyskinesia ◽  
Dopaminergic Neurons ◽  
Neurological Complication ◽  
Carbonyl Stress ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Drug Induced ◽  
Pathophysiological Mechanisms ◽  
The Brain

Purpose. To analyze the results of classical and modern studies reflecting the pathophysiological mechanisms of antipsychotic-induced tardive dyskinesia.Materials and methods. We searched for full-text publications in Russian and English in the databases of E-Library, PubMed, Web of Science and Springer published over the past decade, using keywords (tardive dyskinesia (TD), drug-induced tardive dyskinesia, antipsychotics (AP), neuroleptics, typical antipsychotics, atypical antipsychotics, pathophysiology, etiology and combinations of these words). In addition, the review included earlier publications of historical interest.Results. The lecture proposed theories of development of AP-induced TD, examining its effect on dopaminergic receptors, dopaminergic neurons, neurons of the basal ganglia, and other theories: activation of estrogen receptors, disorders of melatonin metabolism, disorders of the endogenous opioid system, oxidative stress with predominant oxidation processes, blockade of 5-HT2-receptors, a decrease in the pyridoxine level, genetic predisposition, interaction of AP with the brain trace element – iron, carbonyl stress and immune inflammation and the role of the neurotrophic factor.Conclusion. The disclosure of the mechanisms of AP-induced TD will allow the development of a strategy for personalized prevention and therapy of the considered neurological complication of the AP-therapy for schizophrenia in real clinical practice. 

scholarly journals Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences

2021 ◽  
Author(s):  
Galen Ballentine ◽  
Sam Freesun Friedman ◽  
Danilo Bzdok
Keyword(s):  
Large Scale ◽  
Free Form ◽  
Association Cortex ◽  
Receptor Subtypes ◽  
Drug Induced ◽  
Psychological Phenomena ◽  
Input Pole ◽  
Large Scale Networks ◽  
Induced Changes ◽  
The Brain

Psychedelics are thought to alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6,850 free-form testimonials with 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to 3D coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite the variable subjective nature of hallucinogenic experiences, our pattern-learning approach delineated how drug-induced changes of conscious awareness (e.g., dissolving self-world boundaries or fractal distortion of visual perception) are linked to cortex-wide anatomical distributions of receptor density proxies. The dominant explanatory factor related ego-dissolution-like phenomena to a constellation of 5-HT2A, D2, KOR, and NMDA receptors, anchored especially in the brain's deep hierarchy (epitomized by the associative higher-order cortex) and shallow hierarchy (epitomized by the visual cortex). Additional factors captured psychological phenomena in which emotions (5-HT2A and Imidazoline1) were in tension with auditory (SERT, 5-HT1A) or visual (5-HT2A) sensations. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Simultaneously considering many psychoactive molecules and thousands of natural language descriptions of drug experiences our framework finds the underlying semantic structure and maps it directly to the brain. These advances could assist in unlocking their wide-ranging potential for medical treatment.

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