JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brodie, B. B.
Right arrow Articles by Dlabac, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brodie, B. B.
Right arrow Articles by Dlabac, A.
Journal of Pharmacology And Experimental Therapeutics, Vol. 152, Issue 2, 340-349, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics

THE ROLE OF BRAIN SEROTONIN IN THE MECHANISM OF THE CENTRAL ACTION OF RESERPINE

B. B. Brodie 1, M. S. Comer 1, E. Costa 1, and A. Dlabac 1

1 Laboratory of Chemical Pharmacology, National Heart Institute, Bethesda, Maryland

Reserpine sedation is associated with changes in brain serotonin (5-HT) rather than with catecholamines. Thus, after blockade of catecholamine synthesis, catecholamines can be reduced by 80% without producing sedation ; in contrast, reserpine elicits sedation in doses that reduce both 5-HT and catecholamines by only 55%. In addition, there is a time correlation between the effects of reserpine on behavior and impairment of the process that accumulates exogenous 5-HT in brain tissue. This process is recovered in 48 hr when rabbits have recovered from sedation, even though 5-HT stores are still largely depleted. After reserpine, the rate constant of 5-HT efflux is dose-dependent, and is maximal after a dose (5 mg/kg iv.) which depletes 5-HT at a half-life of about 7 min. Intensity and duration of sedation are correlated with initial rates of 5-HT release rather than the final extent of depletion. After doses of reserpine that deplete the monoamines at a maximal rate, the steadystate levels calculated from the rate of synthesis and the rate constant of efflux are 12% of normal for 5-HT and 3% of normal for norcpinephrine (NE). Studies showing that 5-hydroxytryptophan (5-HTP) in doses that elicit excitation also causes the release of brain NE may remove a key argument against the view that reserpine acts through free 5-HT.

Accepted on November 17, 1965




This article has been cited by other articles:


Home page
 ScienceHome page
J. M. Stolk, W. J. Nowack, J. D. Barchas, and S. R. Platman
Brain Norepinephrine: Enhanced Turnover after Rubidium Treatment
Science, April 24, 1970; 168(3930): 501 - 503.
[Abstract] [PDF]

Home page
 ScienceHome page
W. D. Reid, F. J. E. Stefano, S. Kurzepa, and B. B. Brodie
Tricyclic Antidepressants: Evidence for an Intraneuronal Site of Action
Science, April 25, 1969; 164(3878): 437 - 439.
[Abstract] [PDF]

Home page
 ScienceHome page
J. J. Schildkraut and S. S. Kety
Biogenic Amines and Emotion
Science, April 7, 1967; 156(3771): 21 - 30.
[Abstract] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics.