Immunohistochemical study of the serotonergic neuronal system in an animal model of the mood disorder

The monoamine theory is one of the major hypotheses about the biological etiology of major depressive disorders. Recent pharmacological and postmortem investigations suggest that depressed patients have alterations in function of serotonergic neuronal system. However, the exact sites of alterations and the association between these alterations and the etiology of the disorder are still unclear. To elucidate these issues, we immunohistochemically examined vesicle monoamine transporter 2 (VMAT2), serotonin receptor type 1a (5HT1a), and serotonin transporter (5HTT) in the hippocampal region of reserpine-treated rats, an animal model of depression. The results showed more VMAT2-immunoreactive varicose fibers in the pyramidal cell layer of hippocampus and parahippocampal cortexes, and more intense 5HTT-immunoreactivity in the pyramidal cell layer and the area CA4 of hippocampus in the animal models compared to those of the controls. On the other hand, lower density of 5HT1a-immunoreactive deposits in the pyramidal cell layer of hippocampus and the parahippocampal cortex was observed in the animal models compared to those of the controls. These results suggest that a deficit of monoamines induces the alterations in the expression of the storage protein, the receptor and the transporter that are involved in the serotonergic neurotransmission in the hippocampal region. These alterations may underlie the changes of serotonergic system observed in the brains of patients with the depressive disorder.