Serotonin and epilepsy.
In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seizures, although exceptions have been described, too. Conversely, depletion of brain 5-HT lowers the threshold to audiogenically, chemically and electrically evoked convulsions. Furthermore, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. Currently, the role of at least 5-HT(1A), 5-HT(2C), 5-HT(3) and 5-HT(7) receptor subtypes in epileptogenesis and/or propagation has been described. Mutant mice lacking 5-HT(1A) or 5-HT(2C) receptors show increased seizure activity and/or lower threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT(1A) receptors and depolarization of GABAergic neurons by 5-HT(2C) receptors as well as antagonists of 5-HT(3) and 5-HT(7) receptors decrease the excitability in most, but not all, networks involved in epilepsies. Imaging data and analysis of resected tissue of epileptic patients, and studies in animal models all provide evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals with serotonin agonist and/or antagonist properties play a significant role in the pathogenesis of epilepsies.
Bagdy
Gyorgy
G
Laboratory of Neurochemistry and Experimental Medicine, National Institute of Psychiatry and Neurology, Budapest, Hungary. bag13638@mail.iif.hu
Kecskemeti
Valeria
V
Riba
Pal
P
Jakus
Rita
R
D000818:Animals; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000627:therapeutic use
D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin