Original article 491 Investigating the neurobiology of music: brain-derived neurotrophic factor modulation in the hippocampus of young adult mice Francesco Angelucci a , Marco Fiore c , Enzo Ricci b , Luca Padua a , Andrea Sabino b and Pietro Attilio Tonali a It has been shown that music might be able to improve mood state in people affected by psychiatric disorders, ameliorate cognitive deficits in people with dementia and increase motor coordination in Parkinson patients. Robust experimental evidence explaining the central effects of music, however, is missing. This study was designed to investigate the effect of music on brain neurotrophin production and behavior in the mouse. We exposed young adult mice to music with a slow rhythm (6 h/day; mild sound pressure levels, between 50 and 60 db) for 21 consecutive days. At the end of the treatment, mice were tested for passive avoidance learning and then killed for analysis of brain-derived neurotrophic factor (BDNF) and nerve growth factor with enzyme-linked immunosorbent assay (ELISA) in selected brain regions. We found that music-exposed mice showed increased BDNF, but not nerve growth factor in the hippocampus. Furthermore, we observed that music exposure significantly enhanced learning performance, as measured by the passive avoidance test. Our results demonstrate that exposure to music can modulate the activity of the hippocampus by influencing BDNF production. Our findings also suggest that music exposure might be of help in several central nervous system pathologies. Behavioural Pharmacology 18:491–496  c 2007 Lippincott Williams & Wilkins. Behavioural Pharmacology 2007, 18:491–496 Keywords: brain-derived neurotrophic factor, hippocampus, mouse, music, nerve growth factor a Fondazione Don C. Gnocchi, b Institute of Neurology, Catholic University, Largo Gemelli and c Institute of Neurobiology and Molecular Medicine, CNR-EBRI Via del Fosso di Fiorano, Rome, Italy Correspondence to Dr Francesco Angelucci, PhD, Fondazione Don C. Gnocchi, Department of Neuroscience, Institute of Neurology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy E-mail: angeluccifrancesco@rm.unicatt.it Received 13 February 2007 Accepted as revised 19 April 2007 Introduction Music, used as a therapeutic intervention, seems to have a beneficial effect on different symptoms, such as pain (Siedliecki and Good, 2006), anxiety and depression (Hanser and Thompson, 1994; Burns et al., 2002) and nausea (Ezzone et al., 1998). Moreover, it has been observed that music has physiological effects on blood pressure, the cardiac heartbeat and respiration (Knight and Rickard, 2001). The physiological bases of these phenomena are not completely elucidated. Apparently it seems that music can exert physiological effects through the autonomic nervous system (Kemper and Danhauer, 2005), but the factors directly involved are still unknown. In recent years, music has been introduced as a treatment modality for a group of central nervous system (CNS) pathologies extending from disturbed behavior caused by senile dementia (Sung and Chang, 2005) to schizophre- nic-like disorders (Gold et al., 2005) and Alzheimer’s disease (Brotons and Marti, 2003). Recent findings have reported a possible beneficial role of music in some neurological disorders, including Parkinson’s disease (Haneishi, 2001) and cerebral ischemia (Noda et al., 2004). A number of studies using animal models of cerebral trauma have demonstrated that, in an enriched environment combined with multimodal early onset stimulation (including music), the recovery of cerebral functions is greater than that observed in rats exposed to an enriched environment only and/or standard housing (Maegele et al., 2005). These experimental data indicate that exposure to music can influence brain function, probably through modula- tion of neurotransmitters and/or other neuronal media- tors. This hypothesis is supported by data showing that Mozart’s music may modulate dopamine release in the striatum in spontaneously hypertensive rats (Sutoo and Akiyama, 2004) and that loud music potentiates metham- phetamine toxicity in mice (Morton et al., 2001). Other studies in rodents also demonstrate that exposure to music, especially in prenatal and postnatal life, produces long-lasting changes in behavior, probably by modulating the activity of the hippocampus. Thus, music exposure has been reported to improve performance in maze learning in both rats (Rauscher et al., 1998) and mice (Aoun et al., 2005) and increase neurogenesis in the hippocampus of the developing rat brain (Kim et al., 2006). Despite these results, robust experimental evidence explaining the central effects of music is missing. 0955-8810  c 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.