Alterations in Serotonin Neurotransmission in Hyperdopaminergic Rats Lacking the Dopamine Transporter

Abstract

Biogenic amines dopamine (DA) and serotonin (5-HT) are among the most significant monoaminergic neurotransmitters in the central nervous system (CNS). Separately, the physiological roles of DA and 5-HT have been studied in detail, and progress has been made in understanding their roles in normal and various pathological conditions (Parkinson’s disease, schizophrenia, addiction, depression, etc.). In this article we showed that knockout of the gene encoding DAT leads not only to a profound dysregulation of dopamine neurotransmission in the striatum but also in the midbrain, prefrontal cortex, hippocampus, medulla oblongata and spinal cord. Furthermore, significant changes were observed in the production of mRNA of enzymes of monoamine metabolism, as well as to a notable alteration in the tissue level of serotonin, most clearly manifested in the cerebellum and the spinal cord. The observed region-specific changes in the tissue levels of serotonin and in the expression of dopamine and serotonergic metabolism enzymes in rats with an excess of dopamine can indicate important consequences for the pharmacotherapy of drugs that modulate the dopaminergic system. The drugs that affect the dopaminergic system could potently affect the serotonergic system, and this fact is important to consider when predicting their possible therapeutic or side effects.