Elevation of serum prolactin levels after the inhibition ofserotonin uptake

Although earlier investigators showed that serotonin produced an elevation in serum PRL, recent studies indicate that serotonergic mechanisms are not of importance, at least in older adult animals, in the tonic regulation of serum PRL levels. As the activity of neuronal pathways may vary in activity at different chronological ages, the present study was undertaken to further evaluate the role of serotonergic pathways in the regulation of serum PRL levels. During the course of the study, animals in two different weight ranges were studied. In the initial studies, young male rats in the 120- to 170-g range were studied, while in later studies male rats in the 250–340-g weight range were utilized. In rats weighing 120–170 g, the administration of fluoxetine (Lilly 110140), an inhibitor of serotonin uptake, produced a significant elevation of serum PRL which persisted for at least 8 h. At the same time, diencephalon 5-hydroxyindoleacetic acid levels were decreased, providing evidence of the effectiveness of the drug treatment. Methysergide completely blocked the effect of fluoxetine and markedly suppressed serum PRL concentration. In agreement with the results of others, fluoxetine did not produce an increase in serum PRL in older male rats (250–340 g). However, fluoxetine seemed to suppress the circadian elevation of serum PRL in these older rats. These data provide evidence that serotonergic pathways may be of more importance in the tonic regulation of serum PRL in young male Sprague-Dawley rats. The specific pathways involved cannot be determined from these studies.