title: Inhibitory action of morphine on adenosine triphosphatase content in the whole and individual nuclei of mouse brain during the tolerance-dependence development and its reversal by naloxone.
abstract: Fluctuations in the content and distribution of adenosine triphosphatase in the brain of mice during the period of morphine tolerance-dependence development as well as normal and and naloxone induced withdrawal have been studied. The histochemical investigation revealed the enzyme activity in the neurons, neuroglia and blood vessels. In the control animals the nucleus caudatus putamen, globus pallidus, hippocampus, nuclei of amygdala, nuclei hypothalami, substantia grisea centralis, griseum pontis, nucleus trapezoideus, nucleus prepositus hypoglossi, nucleus parabrachialis, nucleus vestibularis, nucleus nervi hypoglossi, nucleus dorsalis nervi vagi, nucleus olivaris and nucleus centralis superior are found to be very rich in ATPase. However, morphine treatment inhibited the enzyme in all the above nuclei and it was linear with the increase in dose and the duration of the treatment. Cytophotometric studies reveal that the differences in the enzymatic activity varies from nuclei to nuclei. Surprisingly enough, normal withdrawal as well as naloxone induced withdrawal significantly elevated the enzyme levels. All above findings have been confirmed biochemically. The study gives a firm support of the earlier finding that morphine inhibits ATPase. In addition to this, the present work also reveals a direct antagonistic effect of naloxone on the content of the enzyme in the morphine treated animals. This suggests that the observed inhibition of the enzyme is narcotic specific. The role of ATPase in the Na+, K+ transport is discussed with respect to morphine action. In the light of the present investigation, the effect of morphine on the neurotransmitter release, and the cause and effect there upon has been analyzed. It has been suggested that ATPase might be the enzyme responsible for the observed pharmacological responses of the neurons to the application of the drug by affecting the Na+, K+ flux and neurotransmitter release.
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003592:Cytophotometry; D004361:Drug Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000201:enzymology*; D009270:Naloxone / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000201:enzymology
chemical_list: D009270:Naloxone; D009020:Morphine; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase