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Published on: January 22, 2016
The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference
Akihiro Mouri1, Yukihiro Noda2, Minae Niwa3
1Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Toyoake 470-1192, Japan; Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya 468-8503, Japan; Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; Japanese Drug Organization of Appropriate Use and Research, Nagoya 468-0069, Japan.
Abstract:
3,4-Methylenedioxymethamphetamine (MDMA) is known to induce dependence and psychosis in humans. Brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity and neurotrophy in midbrain dopaminergic neurons. This study aimed to investigate the role of BDNF in MDMA-induced dependence and psychosis. A single dose of MDMA (10mg/kg) induced BDNF mRNA expression in the prefrontal cortex, nucleus accumbens, and amygdala, but not in the striatum or the hippocampus. However, repeated MDMA administration for 7 days induced BDNF mRNA expression in the striatum and hippocampus. Both precursor and mature BDNF protein expression increased in the nucleus accumbens, mainly in the neurons. Additionally, rapidly increased extracellular serotonin levels and gradually and modestly increased extracellular dopamine levels were noted within the nucleus accumbens of mice after repeated MDMA administration. Dopamine receptor antagonists attenuated the effect of repeated MDMA administration on BDNF mRNA expression in the nucleus accumbens. To examine the role of endogenous BDNF in the behavioral and neurochemical effects of MDMA, we used mice with heterozygous deletions of the BDNF gene. MDMA-induced place preference, behavioral sensitization, and an increase in the levels of extracellular serotonin and dopamine within the nucleus accumbens, were attenuated in BDNF heterozygous knockout mice. These results suggest that BDNF is implicated in MDMA-induced dependence and psychosis by activating the midbrain serotonergic and dopaminergic neurons.
