RELEVANCY OF CHANGES IN CEREBRAL 5-HYDROXYTRYPTAMINE TO RESERPINE-PRODUCED SEDATION

Reserpine-3H and its metabolites are present in the rat brain during sedation and after disappearance of its pharmacological effects. Intracerebrally or intraventricularly administered reserpine-3H shows triphasic efflux and a fairly rapid spread from the site of injection to the same sites in the brain as after its peripheral administration. Centrally injected reserpine (500 μg) did not lower cerebral, but did lower blood 5-hydropytryptamine (5-HT) levels 50 per cent in the first hour. The same amount given intravenously caused 50 per cent depletion of both blood and cerebral 5-HT within 1 hr. Cerebral depletion of 5-HT could not be related to the mobilization of corticos-teroids nor to the inhibition of monoamine oxidase. When administered intracerebrally or intraventricularly, 500 μg reserpine was necessary to induce central effects in rats. This amount is far in excess of that found in the brain of sedated rats after peripheral injection of reserpine. Intracerebrally administered reserpine did not lead to depletion of 5-HT in the brain coincident with sedation. Neither the rate of 5-HT depletion nor the amount of reserpine present in the brain could be correlated with the state of sedation. It is concluded that the reserpine-produced central effects, per se, are not directly related to changes in the cerebral 5-HT content. © 1968.