The Alteration of Brain Metabolism by Narcotic Analgesic Drugs

Clouet, Doris H.

doi:10.1007/978-1-4615-7175-9_20

Cited by 2 publications

(3 citation statements)

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“…For example, morphine has been found to alter the distribution and release of these substances in the brain, and manipulation of the levels of transmitters can modify the pharmacological response to morphine. The evidence for the involvement of one or other of these compounds has recently been reviewed (Clouet, 1971; Way & Shen, 1971;Weinstock, 1971;Way, 1972).…”

Section: Introductionmentioning

confidence: 99%

Morphine and Neurotransmitter Substances: Microiontophoretic Study in the Rat Brain Stem

Bradley¹,

Dray

1974

British J Pharmacology

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The effects of microiontophoretically applied morphine and its interactions with the effects of microiontophoretic applications of either acetylcholine, (–)‐noradrenaline or 5‐hydroxytryptamine have been studied on single neurones in the brain stem of rats anaesthetized with urethane. Morphine excited or inhibited most neurones tested and the effects, especially excitation, were often extremely powerful. However, the time course of the excitatory and inhibitory effects were somewhat different. Desensitization to the excitation produced by morphine was seen after repeated or prolonged applications and it is suggested that this phenomenon may be related to the tolerance which develops after chronic administration of morphine. No desensitization was observed to inhibition of neuronal activity by morphine. Morphine usually reduced the excitation of neurones by acetylcholine, noradrenaline or 5‐hydroxytryptamine but sometimes potentiated the effect, although not always on the same neurones. Inhibition of neuronal activity by these compounds was never modified by morphine and neither were the effects of glutamate or D,L‐homocysteic acid when used as control agonists. The in vitro release of morphine from six micropipettes was determined and the transport number was calculated to be 0.051 (s.d. 0.021). The implications of these observations in explaining the pharmacological actions of morphine are discussed.

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Section: Introductionmentioning

confidence: 99%

Morphine and Neurotransmitter Substances: Microiontophoretic Study in the Rat Brain Stem

Bradley¹,

Dray

1974

British J Pharmacology

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“…It has been suggested that cellular changes in the central nervous system, particularly changes in the disposition and turnover of neurotransmitters (Clouet, 1971) or in receptor sensitivity (Collier, 1965; 1968) may account for the tolerance and physical dependence which results from chronic administration of morphine. We have used the technique of microiontophoresis to study possible changes in the sensitivity of single brain stem neurones to morphine and to certain putative neurotransmitters (acetylcholine, noradrenaline and 5-hydroxytryptamine), in rats following the chronic administration of morphine and also after its withdrawal.…”

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confidence: 99%

“…No significant changes were observed in the initial spontaneous neuronal firing rate or in the qualitative or quantitative effects of acetylcholine, noradrenaline or 5-hydroxytryptamine. However, in chronically treated animals there was a significant decrease in the number of neurones excited by morphine or showing tachyphylaxis to morphine on repeated microiontophoretic applications.We suggest that some of the cellular central nervous system changes which occur during chronic morphine treatment are reflected by the decrease in sensitivity of neurones to morphine excitation.It has been suggested that cellular changes in the central nervous system, particularly changes in the disposition and turnover of neurotransmitters (Clouet, 1971) or in receptor sensitivity (Collier, 1965;1968) may account for the tolerance and physical dependence which results from chronic administration of morphine. We have used the technique of microiontophoresis to study possible changes in the sensitivity of single brain stem neurones to morphine and to certain putative neurotransmitters (acetylcholine, noradrenaline and 5-hydroxytryptamine), in rats following the chronic administration of morphine and also after its withdrawal.…”

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The Effects of Microiontophoretically Applied Morphine and Transmitter Substances in Rats During Chronic Treatment and After Withdrawal From Morphine

Bradley¹,

Dray

1974

British J Pharmacology

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The effects of microiontophoretically applied acetylcholine, noradrenaline, 5-hydroxytryptamine and morphine were studied on single brain stem neurones of rats during chronic morphine pretreatment and 24 h after its withdrawal. No significant changes were observed in the initial spontaneous neuronal firing rate or in the qualitative or quantitative effects of acetylcholine, noradrenaline or 5-hydroxytryptamine. However, in chronically treated animals there was a significant decrease in the number of neurones excited by morphine or showing tachyphylaxis to morphine on repeated microiontophoretic applications.We suggest that some of the cellular central nervous system changes which occur during chronic morphine treatment are reflected by the decrease in sensitivity of neurones to morphine excitation.It has been suggested that cellular changes in the central nervous system, particularly changes in the disposition and turnover of neurotransmitters (Clouet, 1971) or in receptor sensitivity (Collier, 1965;1968) may account for the tolerance and physical dependence which results from chronic administration of morphine. We have used the technique of microiontophoresis to study possible changes in the sensitivity of single brain stem neurones to morphine and to certain putative neurotransmitters (acetylcholine, noradrenaline and 5-hydroxytryptamine), in rats following the chronic administration of morphine and also after its withdrawal.Methods Adult albino rats (350-600 g) were individually housed under the same environmental conditions and received the same diet except for the contents of their drinking fluid. Control animals were given 45% sucrose solution for 21 days. Morphine-treated animals received increasing amounts of the drug (0.5 mg/ml, 1.0 mg/ml and 2.0 mg/ml over successive 7 day periods) dissolved ' Present address: Dept. of Pharmacology, School of Pharmacy, 29/39 Brunswick Square, London WC1N lAX. in 45% sucrose solution. A further group of animals was treated with morphine in the same way but the drug was replaced by sucrose solution 24 h before the experiment. All animals were allowed to drink these solutions ad libitum and their behaviour, fluid intake and body weight were monitored.Following pretreatment the animals were anaesthetized with urethane (1.2-2.4 g/kg) and the cerebellum removed to expose the floor of the 4th ventricle. Spontaneous extracellular activity of single neurones in the pons-medulla was recorded through the central barrel (4 M NaCl) of a five-barrelled glass micropipette. Another barrel contained I M NaCl to monitor current effects, and the remaining barrels contained solutions of the following drugs, at the indicated concentrations and pH: acetylcholine chloride, 0.3 M, pH 4.0-5.0 (Sigma); (-)-noradrenaline bitartrate, 0.12 M, pH 5.0-6.0 (Sigma); 5-hydroxytryptamine (serotonin) bimaleinate, 0.2 M, pH 4.5-5.5 (KochLight); morphine hydrochloride, 0.03 M, pH 4.0-5.0 (Macfarlan Smith Ltd).The effects of the three neurotransmitters, applied in the same order, with a current of 20 nA for...

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The Alteration of Brain Metabolism by Narcotic Analgesic Drugs

Cited by 2 publications

References 98 publications

Morphine and Neurotransmitter Substances: Microiontophoretic Study in the Rat Brain Stem

Morphine and Neurotransmitter Substances: Microiontophoretic Study in the Rat Brain Stem

The Effects of Microiontophoretically Applied Morphine and Transmitter Substances in Rats During Chronic Treatment and After Withdrawal From Morphine

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