Autoradiography reveals selective changes in serotonin binding in neocortex of patients with temporal lobe epilepsy Luisa Rocha a, ⁎ , Lourdes Lorigados-Pedre b , Sandra Orozco-Suárez c , Lilia Morales-Chacón b , Mario Alonso-Vanegas d , Iván García-Maeso b , Juana Villeda-Hernández d , Laura Osorio-Rico d , Bárbara Estupiñán b , Christian Quintana a a Departamento de Farmacobiología, Sede Sur del Centro de Investigación y de Estudios Avanzados, Calz. Tenorios 235, Col. Granjas Coapa, C.P. 14330, México, D.F., Mexico b Centro Internacional de Restauración Neurológica, La Habana, Cuba c Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades del Centro Médico Nacional, México, D.F., Mexico d Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, México, D.F., Mexico Received 22 January 2007; received in revised form 18 April 2007; accepted 19 April 2007 Available online 4 May 2007 Abstract The main goal of the present study was to evaluate binding to serotonin in the neocortex surrounding the epileptic focus of patients with mesial temporal lobe epilepsy (MTLE). Binding to 5-HT, 5-HT 1A , 5-HT 4 , 5-HT 7 receptors and serotonin transporter (5-HTT) in T1–T2 gyri of 15 patients with MTLE and their correlations with clinical data, neuronal count and volume were determined. Autopsy material acquired from subjects without epilepsy (n = 6) was used as control. The neocortex from MTLE patients demonstrated decreased cell count in layers III–IV (21%). No significant changes were detected on the neuronal volume. Autoradiography experiments showed the following results: reduced 5-HT and 5-HT 1A binding in layers I–II (24% and 92%, respectively); enhanced 5-HT 4 binding in layers V–VI (32%); no significant changes in 5-HT 7 binding; reduced 5-HTT binding in all layers (I–II, 90.3%; III–IV, 90.3%, V–VI, 86.9%). Significant correlations were found between binding to 5-HT 4 and 5-HT 7 receptors and age of seizure onset, duration of epilepsy and duration of antiepileptic treatment. The present results support an impaired serotoninergic transmission in the neocortex surrounding the epileptic focus of patients with MTLE, a situation that could be involved in the initiation and propagation of seizure activity. © 2007 Elsevier Inc. All rights reserved. Keywords: Human neocortex; Mesial temporal lobe epilepsy; Serotonin receptors; Serotonin transporter 1. Introduction Serotonin has been shown to be involved in the mechanisms regulating the seizure activity (Bagdy et al., 2007). The idea of inhibition of seizures by serotonin was initially suggested by Bonnycastle et al. (1957), who described that some anticonvulsants, including phenytoin, augment brain serotonin levels. At present, it is known that serotonin may induce inhibitory and excitatory effects on seizure activity. Low extracellular concentrations of serotonin produce protective and anticonvulsant effects, whereas high levels significantly aggravated seizures (Clinckers et al., 2004). Selective inhibitors of the serotonin uptake protect against seizures (Prendiville and Gale, 1993; Pasini et al., 1992; Wada et al., 1993). Concerning serotonin receptor subtypes, the activation of 5- HT 1A receptors plays an inhibitory role on seizure activity (Lopez- Meraz et al., 2005; Wada et al., 1997). Similarly, the serotoninergic neurotransmission mediated by 5-HT 2C receptors suppresses neu- ronal network hyperexcitability and convulsive activity (Tecott et al., 1995; Brennan et al., 1997; Applegate and Tecott, 1998). In contrast, the activation of 5-HT 4 receptors enhances the Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 1208 – 1218 www.elsevier.com/locate/pnpbp Abbreviations: 5-HIIA, 5-hydroxyindolacetic acid; 5-HTT, serotonin transporter; ECoG, electrocorticography; EEG, electroencephalogram; MRI, magnetic resonance imaging; MTLE, mesial temporal lobe epilepsy; PET, positron emission tomography; PMI, post mortem interval; SPECT, single photon emission computed tomography. ⁎ Corresponding author. E-mail address: lrocha@cinvestav.mx (L. Rocha). 0278-5846/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2007.04.014