EVIDENCE THAT TRANQUILIZING ACTION OF RESERPINE IS ASSOCIATED WITH CHANGE IN BRAIN SEROTONIN AND NOT IN BRAIN NOREPINEPHRINE

A reserpine analogue, dimethylaminobenzoyl methylreserpate (Su 5171), can release half the brain norepinephrine in rabbits without releasing significant amounts of brain serotonin and without eliciting sedation. Large doses release about 70% of both amines and induce marked sedation. Additional strong evidence that the sedation produced by reserpine itself is not due to the loss of brain norepinephrine is provided by experiments in which rats and rabbits subjected to stress are not noticeably affected by reserpine. The norepinephrine in the brains of these animals is depleted but serotonin is lowered only slightly. These results suggest that the tranquilizing actions of Rauwolfia alkaloids are related to the change in the level of brain serotonin rather than of norepinephrine. Our studies fail to confirm published observations that reserpine and raunescine in rats release more norepinephrine than serotonin in brain, and that raunescine produces sedation at doses that release considerable brain norepinephrine, but no serotonin. In addition, we are unable to confirm the published observation that Ro 4-1284, a potent benzoquinolizine tranquilizing agent, releases brain serotonin in mice to the same extent as its weakly active congener, Ro 4-1398. The implications of these results to the role of serotonin in the action of reserpine are discussed.