Electroconvulsive shock increases serotonin transporter in the rat frontal cortex Hao-wei Shen 1 , Yohtaro Numachi * ,2 , Sumiko Yoshida, Ko Fujiyama, Shigenobu Toda, Shuichi Awata, Hiroo Matsuoka, Mitsumoto Sato Division of Psychiatry, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan Received 21 September 2002; received in revised form 1 February 2003; accepted 3 February 2003 Abstract The antidepressive action of electroconvulsive shock (ECS) is thought to involve the alteration in serotonin (5-HT) neurotransmission, including the increase in 5-HT release and uptake. In our previous study, 5-HT transporter (5-HTT) mRNA expression was decreased after single and repetitive ECS in rat raphe nucleus. In the present study, we investigated the effects of single and repetitive ECS on the protein levels of 5-HTT in the frontal cortex, hippocampus and raphe nucleus of rat brain using quantitative Western blot analysis. Single ECS did not alter 5-HTT protein expression in any brain regions examined. Repetitive ECS stably increased 5-HTT protein in the frontal cortex, but not in the hippocampus and raphe nucleus. Because ECS is known to facilitate the release of neurotransmitters, our results suggest that the increased 5-HTT protein expression in the frontal cortex might be a compensatory change against the enhanced 5-HT release by ECS in presynaptic terminals. q 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Electroconvulsive shock; Serotonin transporter; Western blotting; Frontal cortex; Hippocampus; Raphe nucleus Electroconvulsive shock (ECS) therapy is a rapid and effective treatment for refractory depression. According to the amine hypothesis of depression, antidepressive action of ECS therapy is considered to involve enhanced serotonin (5- HT) neurotransmission [6,11]. In clinical studies, ECS therapy increases human platelet 5-HT reuptake [9] and imipramine binding sites [7,8]. In animals, ECS increases rat brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations [3,14,16] and the sensitivity of postsynaptic 5-HT1A receptors in the rat hippocampus [2,5]. After its release and action on receptors, 5-HT is reuptaken into presynaptic terminals by 5-HT transporter (5-HTT), and 5- HT neurotransmission is subsequently terminated. There- fore, 5-HTT possibly plays an important role in maintaining a steady state of 5-HT neurotransmission, which is enhanced by ECS. In our previous study [13], 5-HTT mRNA expression was significantly decreased after single and repetitive ECS in the rat raphe nucleus, where B7-9 cell groups containing the cell bodies of 5-HT neurons exist [12]. However, it is still unknown whether ECS changes 5- HTT protein expression in the cell body or terminal region of 5-HT neuron. In the present study, we examined the effects of single and repetitive ECS on 5-HTT protein in the frontal cortex, hippocampus and raphe nucleus of rat using quantitative Western blot analysis. All experiments were performed in accordance with the Guidelines for the Care of Laboratory Animals by the Animal Care Committee of Tohoku University. Adult Sprague–Dawley male rats (SLC Inc., Tokyo, Japan), weighing 190–210 g at the beginning of experiments, were group-housed (eight rats per cage) with food and water ad libitum in a room maintained at 22 ^ 2 8C and 65 ^ 5% humidity under a 12 h light/dark cycle. ECS was administered via ear clip electrodes (70 mA, 0.5 s) to induce a typical tonic-clonic seizure lasting 5 – 10 s. In acute experiments, the animals were decapitated 3, 9 and 24 h after a single ECS. In chronic experiments, ECS was administered every other day, totaling seven shocks. The rats were decapitated 3, 9, 24 h and 2 weeks after the last Neuroscience Letters 341 (2003) 170–172 www.elsevier.com/locate/neulet 0304-3940/03/$ - see front matter q 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0304-3940(03)00178-2 1 Present address: Department of Molecular Psychiatry, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan. 2 Present address: Division of Psychobiology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. * Corresponding author. Tel.: þ81-22-717-7262; fax: þ 81-22-717-7266. E-mail address: ynumachi-thk@umin.ac.jp (Y. Numachi).