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J Neurophysiol 93: 2644-2655, 2005. First published December 29, 2004; doi:10.1152/jn.01181.2004
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Selective Serotonin Reuptake Inhibitors Induce Spontaneous Interneuronal Activity in the Leech Nervous System

María A. Calviño, Irene R. Iscla and Lidia Szczupak

Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Instituto de Fisilogía, Biología Molecular y Neurosciencias–Consejo de Investigaciones Científicas y Técnicas, Ciudad Universitaria, Pabellón II, Buenos Aires, Argentina

Submitted 16 November 2004; accepted in final form 23 December 2004

Serotonin [5-hydroxytryptamine (5-HT)] is a conspicuous neuromodulator of sensory–motor networks that affects a variety of neurons at different levels of the network hierarchy. Because of its many possible targets, it has been difficult to obtain a comprehensive picture of how 5-HT achieves its final modulatory output on any given network. Our hypothesis is that the profile of 5-HT actions is dictated by its pattern of release from endogenous sites. We tested this hypothesis in the leech nervous system by means of a selective serotonin reuptake blocker (SSRI), fluoxetine. Fluoxetine evoked barrages of synaptic potentials in identified sensory, motor, and interneurons. This effect was mimicked by the tricyclic antidepressants imipramine and clomipramine, and by the SSRI citalopram, with relative efficacies that matched their known relative selectivities for the 5-HT transporter. The synaptic responses evoked by fluoxetine in different neurons were temporally correlated, suggesting that they had a common origin. The profile of the synaptic responses matched that expected from the activation of the mechanosensory pressure cells, known to act by polysynaptic pathways. The results suggest that endogenous 5-HT acted on cord spanning interneurons. On the other hand, bath-applied 5-HT evoked an effect different from that of the SSRI. Taken together, the results evidenced that the pattern of action of the monoamine is dictated by the spatial distribution of the 5-HT release sites.


Address for reprint requests and other correspondence: L. Szczupak, LFBM, Ciudad Universitaria. Pabellón II, piso 2, 1428 Buenos Aires, Argentina (E-mail: szczupak{at}mail.retina.ar)




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