Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated the antagonizing effect of aspartic acid on some effects of morphine and on the development of physical dependence on, and tolerance to, morphine. In the present study, we have withdrawal from morphine or administration of a morphine antagonist. For this purpose sixty five white rats were given morphine and aspartic acid separately and in combination in a 5% saccharose solution instead of drinking water for 30 days. Some of the dependent rats were then withdrawn and others were injected with levallorphan. Flying, jumping, wet-dog shaking, body weight loss and motor activity were estimated and free amino acid levels in the brain were determined. Aspartic acid was found to prevent or antagonize the behavioural signs and the changes in the free amino acid levels in the brain. The results are discussed in the light of the previous data.
 ...
PMID:The antagonizing effect of aspartic acid on morphine withdrawal and levallorphan-precipitated abstinence syndrome signs and on associated changes in brain levels of free amino acids in the rat. 10 53

Since it has been shown in previous study that aspartic acid prevents the development of physical dependence on and tolerance to morphine and antagonizes the abstinence syndrom signs, the biochemical bases of that prevention were investigated in the present study. The brain contents of serotonin, DA, NA, and free amino acids of the rats given aspartic acid and morphine separately and in combination were determined. It has been observed that most of the morphine-induced changes in the brain were normalized in the group given aspartic acid and morphine together. The relative ineffectiveness of aspartic acid in normalizing some amino acid levels decreased by morphine was discussed and some logical explanations were found.
 ...
PMID:The antagonizing effect of aspartic acid on the brain levels of monoamines and free amino acids during the development of tolerance to the physical dependence on morphine. 41 14

As free amino acids in the brain have a role in the development of physical dependence on and tolerance to morphine, and in the mechanism of action of some drugs, the effects of aspartic acid which antagonizes some effects of the single dose of morphine were studied during the development of the physical dependence on morphine and after the withdrawal of morphine. 108 rats were given morphine and aspartic acid in different combinations in drinking water for 30 days. Every tenth day the dose of morphine was increased: At the end of this period some of them in each group continued or began to receive aspartic acid depending on the experimental conditions after the withdrawal of morphine. During the experiments body weight, spontaneous motor activity and analgesic threshold were determined. Aspartic acid prevented the alterations induced by morphine during the development of physical dependence and tolerance. Furthermore the rats that received aspartic acid after the withdrawal showed no body weight loss.
 ...
PMID:Antagonizing effect of aspartic acid on the development of physical dependence on and tolerance to morphine in the rat. 57 36

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.
 ...
PMID:Brain asparaginase, ACE activity and plasma cortisol level in morphine dependent rats: effect of aspartic acid and naloxone. 302 85

The aim of this study was to investigate the possible interaction between neuronal cholecystokinin (CCK) and opiate dependence. Rats were made dependent to morphine and the ability of cholecystokinin-octapeptide (CCK-8) and Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2 (BC 264), a selective agonist of CCK-B receptors, to induce signs of morphine withdrawal after ICV injection was tested. Behavioral responses were compared to those occurring during the naloxone-precipitated morphine withdrawal syndrome. In contrast to naloxone, CCK-8 (0.1, 1, and 10 micrograms, ICV) did not precipitate any sign of withdrawal. BC 264 (0.1, 1, and 10 micrograms, ICV) induced a strong hyperlocomotion and wet dog shakes in morphine-dependent rats, the latter effect also observed in nondependent animals. In rats receiving acute morphine, BC 264 induced an opposite effect (i.e., blockade of morphine-induced hyperactivity). Taken together, these results suggest that CCK plays only a minor role in the expression of morphine physical dependence.
 ...
PMID:Effects induced by BC 264, a selective agonist of CCK-B receptors, on morphine-dependent rats. 809 Aug 2