The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Summary Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

The exercising heart at altitude

Maximal cardiac output is reduced in severe acute hypoxia but also in chronic hypoxia by mechanisms that remain poorly understood. In theory, the reduction of maximal cardiac output could result from: (1) a regulatory response from the central nervous system, (2) reduction of maximal pumping capacity of the heart due to insufficient coronary oxygen delivery prior to the achievement of the normoxic maximal cardiac output, or (3) reduced central command. In this review, we focus on the effects that acute and chronic hypoxia have on the pumping capacity of the heart, particularly on myocardial contractility and the molecular responses elicited by acute and chronic hypoxia in the cardiac myocytes. Special emphasis is put on the cardioprotective effects of chronic hypoxia. (Part of a multi-author review.)     

Interaction between delta-6-tetrahydrocannabinol (delta-6-THC) and lithium at the blood brain barrier in rats

Summary Neither the acute nor the chronic i.p. administration of delta-6-tetrahydrocannabinol affected the passage of lithium from blood to brain in normal rats.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat.

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4 degrees C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4 degrees C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

Effect of ethanol on taurine concentration in the brain

Summary The taurine concentration in the brain was decreased in ethanol-dependent rats, but returned to normal soon after withdrawal of ethanol. It was not affected by acute ethanol administration.This research was supported by a grant from the Taisho Pharmaceutical Co., Ltd., Tokyo.     

Morphine suppression of ethanol withdrawal in mice

Summary The acute administration of morphine, alcohol or dopamine results in a pronounced suppression of the convulsions produced by alcohol in mice. The suppressive action of morphine on alcohol withdrawal in the mouse apparently is not a product of morphine intoxication, but rather to some other specific interaction between alcohol and morphine in the central nervous system. The conclusion suggest that dopamine may play a significant role as a modulator in convulsions produced during alcohol withdrawal.Dr.Kenneth Blum is Associate Professor in Pharmacology at The University of Texas Health Science Center at San Antonio and a Career Teacher in Drug Abuse and Alcoholism under a grant number 1-TO1-DA00290-01 from the National Institute on Drug Abuse.Acknowledgments. Our thanks are due toB. Wiggins, R. Marin andS. Elston for their excellent technical assistance. Research funded in part by Air Force Grant No. AFOSR-71-2075.     

Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats.

Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.     

Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats

Summary Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.     

Facilitation or inhibition of memory by morphine: a question of experimental parameters

The effects of morphine on memory are highly controversial. According to some investigators post-trial injections of morphine facilitate memory. Others, however, have reported impairment of memory after morphine injections. To investigate the extent to which this may be due to different experimental parameters, foot-shock intensity and dosage of morphine were systematically varied in a passive-avoidance task. It was found that post-trial administration of medium and relatively high doses of morphine facilitate retention performance following moderate levels of foot-shock. Under other conditions of dose and shock intensity, the drug was not effective or even impaired retention.     

Cardiac output and regional blood flow studies in golden hamsters

Summary A method is described for the acute catheterization of the left ventricle of the heart and descending aorta combined with the use of the radioactive microsphere technique to study hemodynamic parameters in anaesthetized hamsters. The hemodynamic parameters studied include mean blood pressure, cardiac output, percentage distribution of cardiac output and regional blood flows in different organs.     

Facilitation or inhibition of memory by morphine: a question of experimental parameters

Summary The effects of morphine on memory are highly controversial. According to some investigators post-trial injections of morphine facilitate memory. Others, however, have reported impairment of memory after morphine injections. To investigate the extent to which this may be due to different experimental parameters, foot-shock intensity and dosage of morphine were systematically varied in a passive-avoidance task. It was found that post-trial administration of medium and relatively high doses of morphine facilitate retention performance following moderate levels of foot-shock. Under other conditions of dose and shock intensity, the drug was not effective or even impaired retention.Results presented in part at the EBBS Meeting in Louvain-la-Neuve (Belgium), November 1980.     

Role of the Raphe Magnus nucleus in morphine analgesia : studies with intracerebral microinjections in the rat]

Microinjections of low concentration of morphine (5 micrograms) into the nucleus Raphé Magnus of the Rat produce a strong analgesia that can be reversed by systemic naloxone, an opiate antagonist. The administration of naloxone (5 micrograms) into the Raphé Magnus considerably reduces the effects of intravenous morphine. The effects of microinjections of morphine are strongly reduced by Cinanserin, suggesting a role for serotoninergic mechanisms in morphine analgesia.     

Effect of chronic administration of morphine on primary immune response in mice

Summary The effect of 3 different doses of chronically-administered morphine on the primary immune response was studied in mice by estimating spleen/body weight ratio and serum hemolysin production against sheep red blood cells (SRBC). It was observed that morphine exerted a dose-dependent inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. The findings suggest that the inhibitory effect of morphine is specific.     

Structural alterations in normal and axotomized facial nucleus neurons after treatment with morphine.

Chronic morphine administration induced ultrastructural alterations in neurons of the facial nucleus and increased the incidence of cell death after axotomy. These findings may correlate with the significant depression of neuronal metabolism known to occur after opiate treatment.     

Structural alterations in normal and axotomized facial nucleus neurons after treatment with morphine

Summary Chronic morphine administration induced ultrastructural alterations in neurons of the facial nucleus and increased the incidence of cell death after axotomy. These findings may correlate with the significant depression of neuronal metabolism known to occur after opiate treatment.Supported by a grant from the United States Public Health Service, NIDA 5 RO1 DA 0014-06.     

Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells

We have observed that treatment of human glioma cells with morphine in the nanomolar range of concentration affects the mitochondrial membrane potential. The effect is specific to morphine and is mediated by naloxone-sensitive receptors, and is thus better observed on glioma cells treated with desipramine; moreover, the mitochondrial impairment is not inducible by fentanyl or methadone treatment and is prevented by the nitric oxide (NO) synthase inhibitor L-NAME. We conclude that in cultured glioma cells, the morphine-induced NO release decreases the mitochondrial membrane potential, as one might expect based on the rapid inhibition of the respiratory chain by NO. The identification of new intra-cellular pathways involved in the mechanism of action of morphine opens additional hypotheses, providing a novel rationale relevant to the therapy and toxicology of opioids.Received 19 August 2004; received after revision 16 September 2004; accepted 7 October 2004     

Monoamine oxidase activity of the brain of Locusta migratoria in normal conditions and after intoxication by two insecticides: chlordimeform and dieldrin]

Our investigations have shown up an MAO activity in locust brain, by the use of a radio-isotopic method, as much at larval as at adult stage. This MAO activity is in a sample of 34,3 dpm/mg of brain tissue (wet weight). Investigations have also been undertaken on effects of dieldrin and chlordimeform poisoning on this MAO activity. Even at sublethal dosages, chlordimeform causes a significant inhibition of MAO activity in vivo. This finding is in accordance with Beeman and Matsumura's work in vitro. Moreover, acute poisoning by dieldrin produces more than 60% of inhibition of MAO, 3 hours after administration of 115 microng of this insecticide by injection in the hoemocelian cavity.     

Influence of ethanol on calcium, inositol phospholipids and intracellular signalling mechanisms

Studies have implicated Ca++ in the actions of ethanol at many biochemical levels. Calcium as a major intracellular messenger in the central nervous system is involved in many processes, including protein phosphorylation enzyme activation and secretion of hormones and neurotransmitters. The control of intracellular calcium, therefore, represents a major step by which neuronal cells regulate their activities. The present review focuses on three primary areas which influence intracellular calcium levels; voltage-dependent Ca++ channels, receptor-mediated inositol phospholipid hydrolysis, and Ca++/Mg++-ATPase, the high affinity membrane Ca++ pump. Current research suggests that a subtype of the voltage-dependent Ca++ channel, the dihydropyridine-sensitive Ca++ channel, is uniquely sensitive to acute and chronic ethanol treatment. Acute exposure inhibits, while chronic ethanol exposure increases 45Ca++-influx and [3H]dihydropyridine receptor binding sites. In addition, acute and chronic exposure to ethanol inhibits, then increases Ca++/Mg++-ATPase activity in neuronal membranes. Changes in Ca++ channel and Ca++/Mg++-ATPase activity following chronic ethanol may occur as an adaptation process to increase Ca++ availability for intracellular processes. Since receptor-dependent inositol phospholipid hydrolysis is enhanced after chronic ethanol treatment, subsequent activation of protein kinase-C may also be involved in the adaptation process and may indicate increased coupling for receptor-dependent changes in Ca++/Mg++-ATPase activity. The increased sensitivity of three Ca++-dependent processes suggest that adaptation to chronic ethanol exposure may involve coupling of one or more of these processes to receptor-mediated events.