Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Rewarding deep brain stimulation at the medial forebrain bundle favours avoidance conditioned response in a remote memory test, hinders extinction and increases neurogenesis Gemma Huguet b , Elisabet Kádár b, **, Noelia Serrano a,1 , Carles Tapias-Espinosa a,2 , Soleil García-Brito a , Ignacio Morgado-Bernal a , Laura Aldavert-Vera a , Pilar Segura-Torres a, * a Universitat Autònoma de Barcelona, Departament de Psicobiologia i de Metodologia de les Ciències de la Salut, Institut de Neurociències, 08193 Bellaterra, Barcelona, Spain b Universitat de Girona, Departament de Biologia. 17003 Girona, Spain ARTICLE INFO Keywords: Intracranial self-stimulation Deep brain stimulation Medial forebrain bundle Active avoidance Long-term memory Extinction Neurogenesis ABSTRACT Intracranial Self-Stimulation (ICSS) at the medial forebrain bundle consistently facilitates learning and memory in rats when administered post-training or when administered non-concurrent to training, but its scope re- garding remote memory has not yet been studied. The present work aims to test whether the combination of these two forms of ICSS administration can cause a greater persistence of the facilitating effect on remote re- tention and affect neurogenesis in the dentate gyrus (DG) of the hippocampus. Rats were trained in active avoidance conditioning and tested in two retention sessions (10 and 90 days) and later extinction. Subjects received an ICSS session after each of the five avoidance acquisition sessions (post- training treatment) and half of them also received ten additional ICSS sessions during the rest period between retention tests (non-concurrent treatment). All the stimulated groups showed a higher performance in acquisi- tion and retention sessions, but only the rats receiving both ICSS treatments showed greater resistance to ex- tinction. Remarkably, at seven months, rats receiving the non-concurrent ICSS treatment had a greater number of DCX-positive cells in the DG as well as a higher amount of new-born cells within the granular layer compared to rats that did not receive this additional ICSS treatment. Our present findings significantly extend the temporal window of the facilitating effect of ICSS on active avoidance and demonstrate a neurogenic effect of rewarding medial forebrain bundle stimulation. 1. Introduction Long-term memory plays a key role in the psychological well-being of individuals and increases their adaptive possibilities in the future. Memory consolidation can be affected by multiple variables, including the subject’s motivational state. Activation of neuroanatomical areas of the reward system through deep brain stimulation (DBS), not only manages to generate appetitive responses, but it also modulates memory systems, affecting both their physiology and the behavioural outcome associated to their function. In fact, activation of the lateral hypothalamus at the medial forebrain bundle (MFB) via intracranial electrical self-stimulation (ICSS), a form of rewarding DBS regulated by the subjects themselves, has been proven to consistently facilitate learning and memory, in both implicit [1][2], and explicit [3] tasks, in rats. However, the anatomical structures mediating this memory-im- proving action are not yet fully specified. Effects of MFB-ICSS in two-way active avoidance (TWAA), an emotional conditioning task that involves an implicit memory, have been extensively studied. It has been shown that post-training ICSS enhances TWAA memory consolidation and improves retention https://doi.org/10.1016/j.bbr.2019.112308 Received 9 July 2019; Received in revised form 15 October 2019; Accepted 15 October 2019 ⁎ Corresponding author at: Departament de Psicobiologia de les Ciències de la Salut. Edifici B. Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. ⁎⁎ Corresponding author at: Departament de Biologia. Universitat de Girona. Carrer Maria Aurèlia Capmany, 40, 17003 Girona, Spain. E-mail addresses: elisabet.kadar@udg.edu (E. Kádár), pilar.segura@uab.cat (P. Segura-Torres). 1 Universidad Politécnica de Madrid. Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology. 28223 Pozuelo de Alarcón, Madrid, Spain (current address). 2 Universitat Autònoma de Barcelona, Departament de Psiquiatria i de Medicina Legal, Institut de Neurociències. 08193 Bellaterra, Barcelona, Spain (current address). Behavioural Brain Research xxx (xxxx) xxxx 0166-4328/ © 2019 Elsevier B.V. All rights reserved. Please cite this article as: Gemma Huguet, et al., Behavioural Brain Research, https://doi.org/10.1016/j.bbr.2019.112308