Epilepsy and dopaminergic system

Epilepsy is accompanied with a strong change in neuronal activity not only in excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission, but also in neuromodulatory agents. Dopaminergic system, as an important neuromodulatory system of the brain, has significant effect on neuronal excitability. In addition, this system undergoes many changes in epileptic brain. Understanding the effects of dopaminergic system in neuronal activities in epileptic brain and knowing the seizure-induced changes in dopaminergic system can shed light into finding the mechanisms involved in epileptogenesis and can help us in finding new treatments for epilepsy. In this review we briefly introduce dopaminergic system and its changes in brain areas which have role in epilepsy. Then, we will focus on the evidences showing the relationship between epilepsy and dopaminergic system. D ow nl oa de d fr om p pj .p hy ph a. ir at 1 :0 8 + 04 30 o n M on da y Ju ne 1 5t h 20 20 Epilepsy and dopaminergic system Physiol Pharmacol 21 (2017) 1-14 | 2 dysfunctions. Therefore, understanding the effects of dopaminergic system in neuronal activities in epileptic brain and knowing the seizure-induced changes in dopaminergic system can shed light into finding the mechanisms involved in epileptogenesis and can help us in finding new treatments for epilepsy. In this review we will briefly introduce dopaminergic system and its changes in brain areas which have role in epilepsy. Then, we will focus on the evidences showing the relationship between epilepsy and dopaminergic system. Dopamine receptors Dopamine is one of the most important modulatory neurotransmitters in the central nervous system which is released from dopaminergic fibers. There are four main dopaminergic pathways in central nervous system including: 1) the nigrostriatal, 2) mesolimbic, 3) mesocortical and 4) tuberoinfundibular systems (Fig. 1) (Koob, 1992). Based on sequence homology, pharmacology and second messenger activation, dopamine receptors are divided into two subfamilies: D1 -like and D2 -like receptors. The D1Table 1: Cell signaling pathways of dopaminergic receptors Reference Signaling pathway Cellular effector Coupled G proteins Dopamine receptors (Beaulieu and Gainetdinov 2011) Increasing cAMP Adenylyl cyclase, Protein kinase A stimulation Gαs/Gαolf