Summary
The phosphodiesterase inhibitor and putative antidepressant rolipram (0.3–30 mg/kg i.p.) stimulated the accumulation of dopa following inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl dose-dependently in all brain regions investigated, suggesting that both dopamine and noradrenaline synthesis was enhanced. The stimulatory effect of rolipram on dopa accumulation in dopamine rich regions persisted even after pretreatment with γ-butyrolactone which by itsself increased dopa accumulation three fold.
Following inhibition of catecholamine synthesis with α-amethyl-p-tyrosine rolipram accelerated the disappearance of noradrenaline and slowed the disappearance of dopamine. At low doses rolipram tended to reduce the pargyline-induced accumulation of 3-methoxytyramine.
Rolipram attenuated the accumulation of 5-hydroxytryptophan in the neocortex and the diencephalon of 3-hydroxybenzylhydrazine HCl pretreated rats.
The data suggest that rolipram enhances noradrenergic transmission by direct stimulation of tyrosine hydroxylase and by an increase of neuronal activity. Despite a stimulatory effect on tyrosine hydroxylase rolipram does not appear to alter dopamine release and metabolism to a large extent. In view of the occurrence of head-twitches the rolipram-induced reduction of 5-hydroxytryptamine metabolism may be due to feedback inhibition.
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Parts of this communication have been presented at the Joint meeting of the French and German Pharmacological Societies in Freiburg, Federal Republic of Germany, September 1983, and at the 14th C.I.N.P. meeting in Florence, June 1984.
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Kehr, W., Debus, G. & Neumeister, R. Effects of rolipram, a novel antidepressant, on monoamine metabolism in rat brain. J. Neural Transmission 63, 1–12 (1985). https://doi.org/10.1007/BF01249580
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DOI: https://doi.org/10.1007/BF01249580