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Research ArticleArticle

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

B. B. Brodie, M. S. Comer, E. Costa and A. Dlabac
Journal of Pharmacology and Experimental Therapeutics May 1966, 152 (2) 340-349;
B. B. Brodie
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M. S. Comer
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E. Costa
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A. Dlabac
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Abstract

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.

Footnotes

    • Accepted November 17, 1965.
  • The Williams & Wilkins Comapny

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Journal of Pharmacology and Experimental Therapeutics
Vol. 152, Issue 2
1 May 1966
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Research ArticleArticle

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

B. B. Brodie, M. S. Comer, E. Costa and A. Dlabac
Journal of Pharmacology and Experimental Therapeutics May 1, 1966, 152 (2) 340-349;

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Research ArticleArticle

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

B. B. Brodie, M. S. Comer, E. Costa and A. Dlabac
Journal of Pharmacology and Experimental Therapeutics May 1, 1966, 152 (2) 340-349;
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