CLINICAL ASPECTS AMT, v. II, no. 3, 2013, p. 272 NICOTINE DISPLAYS ANTIDEPRESSANT ACTIVITY DURING THE RAT FORCED SWIMMING TEST RADU IONUŢ BRAGA 1 , MIHAI AURELIAN GHIŢĂ 2 , MIRCEA LUPUȘORU 3 , GABRIELA ELENA LUPUŞORU 4 , LEON ZĂGREAN 5 1,2,3,5 “Carol Davila” University of Medicine and Pharmacy București, 3 “Dr. Constantin Gorgoş” Titan Psychiatric Hospital București, 4 “Sf. Ioan” Emergency Hospital Bucureşti Keywords: forced swimming test, mecamylamine, nicotine, serotonin Abstract: Nicotine addiction is frequent in people with mood disorders; however the mechanisms involved in nicotine action are not well understood, despite numerous electrophysiological, pharmacological and behavioural studies. The present study investigates the antidepressant effect of nicotine on 30 male Wistar rats divided into three groups: nicotine, nicotine plus mecamylamine and control. The rats were exposed after substance administration to the forced swimming test, the most predictive and widely used animal test for antidepressant action. The results showed a significant increase in swimming activity, a reduction of immobility activity and a delay in immobility latency. The effects of nicotine were blocked by mecamylamine administration. The study demonstrates that acute nicotine administration induces the activation of serotonergic neurons, acting as an antidepressant pharmacological agent. Cuvinte cheie: testul înotului forțat, mecamilamină, nicotină, serotonină Rezumat: Dependența de nicotină este frecvent întâlnită la pacienții cu tulburări de dispoziție, totuși mecanismele implicate în acțiunea nicotinei sunt încă insuficient cunoscute, în ciuda numeroaselor studii de electrofiziologie, farmacologie și comportament din literatură. Studiul prezent investighează efectul antidepresiv al nicotinei pe un număr de 30 de șobolani Wistar, împărțiți în trei loturi: nicotină, nicotina plus mecamilamină și control. După administrarea substanțelor, animalele au fost expuse testului de înot forțat, cel mai răspândit și mai predictiv test utilizat pentru demonstrarea efectelor antidepresive la animal. Rezultatele demonstrează o creștere semnificativă a timpului de înot, o reducere a imobilității și o creștere a latenței imobilității. Efectele induse de nicotină au fost inhibate în situația administrării mecamilaminei. Studiul prezent demonstrează că administrarea acută a nicotinei conduce la activarea neuronilor serotonergici și acționează ca un agent farmacologic antidepresiv. 1 Corresponding author: Mircea Lupuşoru, Bd. Eroii Sanitari, Nr. 8, Cod 050474 București, România, E-mail: mircealupusoru@yahoo.com, Tel/Fax: +4021 3412031 Article received on 03.04.2013 and accepted for publication on 14.06.2013 ACTA MEDICA TRANSILVANICA September 2013;2(3):272-274 INTRODUCTION Tobacco smoking is probably the most widespread and persistent addiction in humans and is driven by nicotine in tobacco smoke. Over the last several decades, numerous studies have investigated the molecular genetics, pharmacology, electrophysiology and behaviour in nicotine reinforcement. Although several treatments have been designed for smoking cessation, smoking motivations like the ability to control symptoms of anxiety and depression or the desire to control appetite are not fully understood in terms of functional mechanisms.(1) Serotonin (5-HT) neurons are located mainly in the raphe nuclei of the brain stem and provide the majority of 5-HT innervations to the forebrain. Their function is associated to wide spectrum of actions in the nervous system by modulating neural development, synaptic plasticity, pain sensation, rhythm, food intake and a variety of behaviours.(2-4) It has been proposed that perturbation of the 5-HT level in the brain contributes to depression and anxiety.(5,6) Several lines of evidence suggest that forebrain 5-HT contributes to acute and chronic nicotine exposure. Nicotine increases the firing rate of neurons located in the raphe nuclei and leads to a rise in extracellular 5-HT in some regions of the forebrain.(7,8) Direct administration of nicotine to the dorsal raphe nuclei (DRN) demonstrated clear anxiolytic effects (9). Certain studies point nicotine to be involved in the onset of depression secondary to the suppression of 5-HT transporters (10) and the inhibition of 5-HT 3 receptors.(11) The forced swimming test (FST) is a common behavioural test for assessing depression in rodents and testing the efficiency of anti-depressant drugs. Despite some limitations, the FST is currently the most widely used preclinical in-vivo test of antidepressant efficacy.(12,13) PURPOSE The aim of the current study is to investigate the effects of nicotine acute administration on a rat model of depression, involving the forced swimming test. To validate the behavioural effects of nicotine, mecamylamine hydrochloride, a noncompetitive nicotinic acetylcholine receptor antagonist was also administered.