Paper Information

Title:  INVOLVEMENT OF THE ENZYME 5ALPHA-REDUCTASE IN PAIN INDUCED CNS TESTOSTERONE ELIMINATION, MORPHINE INDUCED ANALGESIA AND DEPENDENCE, AND REWARDING SYSTEM
Type: PAPER
Author(s): HOSSEINI A.,VERDI J.,AHMADIAN A.A.H.*
 
 *DEPARTMENT OF PHARMACOLOGY, NEUROSCIENCE RESEARCH CENTER, SHAHEED BEHESHTI UNIVERSITY (MEDICAL SCIENCES)
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Interaction between testosterone and morphine and its effects on pain have been under investigation for many years. Testosterone is now considered as neurosteroid which can be produced by brain apart from gonads. The enzyme 5alpha-reductase (5a-R), a metabolizing enzyme for testosterone, has a wide distribution in the brain and spinal cord. Since both chronic pain and morphine reduce testosterone levels in the CNS, we become interested in study of the enzyme 5a-R. Early studies showed that both morphine and chronic pain reduce brain testosterone levels more than serum and this effect is inhibited by finasteride (an inhibitor of 5a-R) and probably shows an increased activity of the enzyme by morphine and pain. This conclusion was confirmed by study of changes in the enzyme mRNA levels, since it was founded that acute and chronic morphine administration increase the enzyme mRNA levels. The question was raised whether the increase in 5a-R activity following morphine has a role in expression or modulation of morphine’s effects. Behavioral studies showed that the enzyme inhibition increases morphine-induced analgesia and decreases tolerance and dependence. Microdialysis studies were performed in the nucleus accumbens (center for brain rewarding system and action of addictive drugs). The enzyme inhibition blocked morphine-induced increase in the metabolites of dopamine. Taken together, these data show the involvement of the enzyme 5a-R in the in pain induced CNS testosterone elimination, morphine induced analgesia and dependence, and rewarding system.

 
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