title: Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice.
abstract: Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperitoneal injection of mefloquine in mice, when coupled to subthreshold social defeat stress, is sufficient to produce depression-like social avoidance behavior. Direct infusion of mefloquine into the nucleus accumbens (NAc), a key brain reward region, increased stress-induced social avoidance and anxiety behavior. In contrast, infusion into the ventral hippocampus had no effect. Whole cell recordings from NAc medium spiny neurons indicated that mefloquine application increases the frequency of spontaneous excitatory postsynaptic currents, a synaptic adaptation that we have previously shown to be associated with increased susceptibility to social defeat stress. Together, these data demonstrate a role for the NAc in mefloquine-induced depression and anxiety-like behaviors.
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Mitra
authors.initials: M
authors.lastname: Heshmati
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Sam A
authors.initials: SA
authors.lastname: Golden
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Madeline L
authors.initials: ML
authors.lastname: Pfau
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Christoffel
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Elena L
authors.initials: EL
authors.lastname: Seeley
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cahill
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Lena A
authors.initials: LA
authors.lastname: Khibnik
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: scott.russo@mssm.edu.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015767:Mefloquine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D013315:Stress, Psychological / Q000139:chemically induced*
chemical_list: D015767:Mefloquine
keywords: Anxiety; Depression; Mefloquine; Nucleus accumbens; Social defeat stress