Catecholamine and 5-hydroxytryptamine synthesis and metabolism following intracerebroventricular injection of dibutyryl cyclic AMP.

Two to seven days after bilateral implantation of polyethylene tubings into the lateral ventricles rats were injected intracerebroventricularly with dibutyryl cAMP or dibutyryl cGMP. The accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhyrazine HCl, served as a measure of catecholamine and 5-hydroxytryptamine synthesis in vivo. A dose of 100 microgram dibutyryl cAMP per rat but not dibutyryl cGMP increased the accumulation of dopa in all brain regions by 70 to 130%. Both nucleotides stimulated the formation of 5-hydroxytryptophan in the dopamine-rich part of the limbic system and diencephalon and in addition dibutyryl cAMP increased 5-hydroxytryptophan in C. striatum and cerebellum. Dibutyryl cAMP (25-200 microgram per rat) did not change the dopamine levels in the dopamine-rich parts of the brain but decreased the noradrenaline level of the C. striatum in a dose-dependent manner. The same doses of dibutyryl cAMP elevated the 5-hydroxytryptamine level in brain stem and the level of 5-hydroxyindole acetic acid in diencephalon and the limbic system. The disappearance of noradrenaline but not of dopamine after inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine methylester HCl was accelerated in most brain regions. The data are compatible with the view that dibutyryl cAMP stimulates tyrosine and tryptophan hydroxylase directly. In addition, dibutyryl cAMP appears to enhance the utilization of noradrenaline but not that of dopamine. The increased utilization of 5-hydroxytryptamine may be restricted to the diencephalon and the limbic system.