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 regions of the rat brain utilizing an autoradiographic method and alpha[14C]methyl-L-tryptophan as a tracer after an acute treatment with reserpine (10 mg/kg IP) or NSD-1015 (m-hydroxybenzylhydrazine) (100 mg/kg 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) decrease in the rate of 5-HT synthesis in a large number of discrete brain structures. Reserpine had no influence on the plasma concentration of amino acids sharing the same carrier with tryptophan nor on the fraction of plasma-free tryptophan. NSD-1015 induced a statistically significant increase (p < .05) in the rate of 5-HT synthesis in 20 out of 28 brain regions but produced a pronounced decrease in the rate of 5-HT synthesis 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 the form of 5-hydroxy-alpha[14C]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 from other brain structures as result of reserpine are also given. NSD-1015 treatment also induced a time-dependent increase in the plasma concentration of free tryptophan that becomes significant 30 minutes after NSD-1015 injection. Our results suggest that reserpine induces a decrease in 5-HT synthesis probably via direct or indirect inhibition of tryptophan hydroxylase activity. Since NSD-1015 alone increased the rate of 5-HT synthesis, the measurement of 5-HT synthesis in previous experiments using NSD-1015 and measuring the rate of 5-hydroxytryptophan accumulation after NSD-1015 induced inhibition of decarboxylase activity should be interpreted with reservation.
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Laboratory for Molecular Neuropharmacology, Ruder Bosković Institute, Zagreb, Croatia.
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D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000096:biosynthesis*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D012701:Serotonin; D012110:Reserpine; C004297:3-hydroxybenzylhydrazine