Noradrenergic modulation of serotonin synthesis and metabolism. II. Stimulation by 3-isobutyl-1-methylxanthine.

The hypothesis that norepinephrine neurons facilitate serotonin metabolism was tested by employing the adenosine antagonist 3-isobutyl-1-methylxanthine (IBMX) as a pharmacological probe to enhance central noradrenergic metabolism. IBMX elevated brain concentrations of 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid and increased the accumulation rates of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan. Maximal effects were observed 3 hr after drug administration, with 14 mg/kg of IBMX. The effects of IBMX on serotonin metabolism were observed in cortex, striatum and hippocampus, antagonized by clonidine and propranolol and prazosin and absent in animals whose norepinephrine neurons had been destroyed with 6-hydroxydopamine. The data are discussed in terms of a noradrenergic facilitation of serotonin turnover.