Clomipramine-induced serum prolactin as a marker for serotonin and dopamine turnover: results of an open label study
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Central nervous system (CNS) monoamine deficits have been linked to a number of pathological conditions such as major depressive disorder. Individual biological variations in 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) might account for the variation in responses of neurotransmitter systems observed after the administration of clomipramine. The prolactin response to clomipramine has been widely used to assess CNS functioning. This open label study investigates the prolactin response induced by clomipramine in the plasma of healthy volunteers and whether it is related to changes in monoamine metabolites. The effects of clomipramine challenge on prolactin, 5-HIAA, HVA and MHPG were measured in 12 healthy volunteers. Samples were drawn directly before and 50 min after clomipramine infusion. A statistically significant increase in serum prolactin concentrations was measured in women 50 min after CMI infusion, but not in men. We found no significant increases in the serum monoamine metabolite concentrations 50 min after CMI infusion. Changes in HVA and 5-HIAA correlated statistically significantly and positively with the amount of prolactin release in the whole sample. Furthermore, positive correlations were found between ∆50–0 min 5-HIAA and ∆50–0 min HVA, although we did not find a correlation between ∆50–0 min prolactin and ∆50–0 min MHPG after clomipramine challenge. The pronounced prolactin release in healthy adult women might indicate a higher physiological sensitivity. Correlations between intra-individual changes in HVA, 5-HIAA and serum prolactin might indicate a central nervous effect of clomipramine on monoamine turnover. We conclude that monoamine changes in relation to prolactin response after clomipramine challenge may be suitable for characterizing the relationship between central serotonergic and dopaminergic function.
KeywordsClomipramine challenge Homovanillic acid Prolactin Monoamine metabolites Plasma
The authors thank Klaus Krieger, Ph.D. and Margit Geisler for performing the biochemical analyses and Raimund Schneider, Ph.D. and Prof. Erlo Lehmann, Ph.D. for their helpful suggestions. The authors further acknowledge the essential statistical support provided by Wolfgang Meyer, Ph.D. (Zentralinstitut für angewandte Mathematik, Research Center Jülich). The present work was supported by the Pinguin Stiftung. This funding source had no influence on the study design, the collection, analysis and interpretation of data, the writing of the report or on the decision to submit the paper for publication.
Conflict of interest
Pharmaceutical companies were involved in supporting the speakers’ honoraria, travel funds, advisory panel payments and research grants. There were, however, no competing interests related directly to the subject of this paper. All authors declare that they have no conflicts of interest.
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