THE ACUTE EFFECTS OF RESERPINE AND NSD-1015 ON THE BRAIN-SEROTONIN SYNTHESIS RATE MEASURED BY AN AUTORADIOGRAPHIC METHOD

The rate of serotonin (5-HT) synthesis was measured in the discrete re gions of the rat brain utilizing an autoradiographic method and alpha[ C-14] methyl-L-tryptophan as a tracer after an acute treatment with re serpine (10 mg/kg IP) or NSD-1015 (m-hydroxybenzylhydrazine) (100 mg/k g IP). Controls were injected with the same volume of solvent in place of reserpine or NSD-1015. Our results showed that reserpine induced a statistically significant (except for medial geniculate body) decreas e in the rate of 5-HT synthesis in a large number of discrete brain st ructures. Reserpine had no influence on the plasma concentration of am ino acids sharing the same carrier with tryptophan nor on the fraction of plasma-free tryptophan. NSD-1015 induced a statistically significa nt increase (p < .05) in the rate of 5-HT synthesis in 20 out of 28 br ain regions but produced a pronounced decrease in the rate of 5-HT syn thesis in the pineal body. This decrease in the pineal body serotonin synthesis rate is most likely the result of the loss of the label in t he form of 5-hydroxy-alpha[C-14]methyl-L-tryptophan [5-OHMTrp] that is not metabolized further because aromatic amino acid decarboxylase was inhibited. The data showing that there was no loss of the 5-OHMTrp fr om other brain structures as result of reserpine ave also given. NSD-1 015 treatment also induced a time-dependent increase in the plasma con centration of free tryptophan that becomes significant 30 minutes afte r NSD-1015 injection. Our results suggest that reserpine induces a dec rease in 5-HT synthesis probably via direct or indirect inhibition of tryptophan hydroxylase activity. Since NSD-1015 alone increased the ra te of 5-HT synthesis, the measurement of 5-HT synthesis in previous ex periments using NSD-1015 and measuring the rate of 5-hydroxytryptophan accumulation after NSD-1015 induced inhibition of decarboxylase activ ity should be interpreted with reservation.