PT  - JOURNAL ARTICLE
AU  - B. B. Brodie
AU  - M. S. Comer
AU  - E. Costa
AU  - A. Dlabac
TI  - THE ROLE OF BRAIN SEROTONIN IN THE MECHANISM OF THE CENTRAL ACTION OF RESERPINE
DP  - 1966 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 340--349
VI  - 152
IP  - 2
4099  - http://jpet.aspetjournals.org/content/152/2/340.short
4100  - http://jpet.aspetjournals.org/content/152/2/340.full
SO  - J Pharmacol Exp Ther1966 May 01; 152
AB  - 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. The Williams & Wilkins Comapny