Brain asparaginase, ACE activity and plasma cortisol level in morphine dependent rats: effect of aspartic acid and naloxone.
The activities of the brain L-asparaginase and angiotensin converting enzyme (ACE), and the plasma cortisol level were found to be decreased in the rats implanted with morphine (M) containing pellets. Even though 10 mg/kg of naloxone (N) itself showed an inhibitory effect on ACE it abolished the inhibitions seen in the M dependent rats five min following subcutaneous injection. The chronic administration of L-aspartic acid (ASP) during the development of physical dependence or just before the N injection prevented the increase of the plasma cortisol caused by N. It is concluded that in addition to the inhibition of the brain L-asparaginase activity which was previously hypothesized to be the main reason of the development of physical dependence on opiates as a result of the related experimental and clinical data, the inhibition by M of the brain ACE activity may take part in the development of physical dependence. With regard to the plasma cortisol level, the concomitant administration of ASP with M blocks, to a great extent, the development of physical dependence on opiate. The single dose of ASP administration before N injection prevents the effect of N, the manifestation of abstinence syndrome.
D000818:Animals; D001215:Asparaginase / Q000378:metabolism*; D001224:Aspartic Acid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001224:Aspartic Acid; D009270:Naloxone; D009020:Morphine; D007703:Peptidyl-Dipeptidase A; D001215:Asparaginase; D006854:Hydrocortisone