title: Rapid and lasting enhancement of dopaminergic modulation at the hippocampal mossy fiber synapse by electroconvulsive treatment.
abstract: Electroconvulsive therapy (ECT) is an established effective treatment for medication-resistant depression with the rapid onset of action. However, its cellular mechanism of action has not been revealed. We have previously shown that chronic antidepressant drug treatments enhance dopamine D1-like receptor-dependent synaptic potentiation at the hippocampal mossy fiber (MF)-CA3 excitatory synapse. In this study we show that ECT-like treatments in mice also have marked effects on the dopaminergic synaptic modulation. Repeated electroconvulsive stimulation (ECS), an animal model of ECT, strongly enhanced the dopamine-induced synaptic potentiation at the MF synapse in hippocampal slices. Significant enhancement was detectable after the second ECS, and further repetition of ECS up to 11 times monotonously increased the magnitude of enhancement. After repeated ECS, the dopamine-induced synaptic potentiation remained enhanced for more than 4 wk. These synaptic effects of ECS were accompanied by increased expression of the dopamine D1receptor gene. Our results demonstrate that robust neuronal activation by ECS induces rapid and long-lasting enhancement of dopamine-induced synaptic potentiation at the MF synapse, likely via increased expression of the D1receptor, at least in part. This rapid enhancement of dopamine-induced potentiation at the excitatory synapse may be relevant to the fast-acting antidepressant effect of ECT.
  
  
  
  We show that electroconvulsive therapy (ECT)-like stimulation greatly enhances synaptic potentiation induced by dopamine at the excitatory synapse formed by the hippocampal mossy fiber in mice. The effect of ECT-like stimulation on the dopaminergic modulation was rapidly induced, maintained for more than 4 wk after repeated treatments, and most likely mediated by increased expression of the dopamine D1 receptor. These effects may be relevant to fast-acting strong antidepressant action of ECT.
authors: Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; kkatsu-tky@umin.ac.jp.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Saitama, Japan.
authors: Katsunori
authors: K
authors: Kobayashi
authors: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors: Yuki
authors: Y
authors: Imoto
authors: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors: Fumi
authors: F
authors: Yamamoto
authors: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors: Mayu
authors: M
authors: Kawasaki
authors: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors: Miyuki
authors: M
authors: Ueno
authors: Center for Integrative Education in Pharmacy and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; and.|Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors: Eri
authors: E
authors: Segi-Nishida
authors: Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Saitama, Japan.
authors: Hidenori
authors: H
authors: Suzuki
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects* / Q000528:radiation effects; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D010879:Piperazines; D011500:Protein Synthesis Inhibitors; D011954:Receptors, Dopamine; D003513:Cycloheximide; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D003975:Diazepam; D004298:Dopamine
keywords: antidepressant; dopamine; electroconvulsive therapy; hippocampus; mossy fiber