The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization.
Akihiro Mouri, Yukihiro Noda, Minae Niwa, Yurie Matsumoto, Takayoshi Mamiya, Atsumi Nitta, Kiyofumi Yamada, Shoei Furukawa, Tatsunori Iwamura, Toshitaka Nabeshima
Behavioural Brain Research May 1, 2017 DOI: 10.1016/j.bbr.2017.04.052 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice, including wild-type and BDNF heterozygous knockout mice |
| Interventions | 3 4-Methylenedioxymethamphetamine (MDMA) dopamine receptor antagonists |
| Dose | 10 mg/kg |
| Duration | Single dose; repeated administration for 7 days |
| Topics | Serotonin MDMA |
| Keywords | Animals Mice, inbred c57bl Mice, knockout Raclopride N-methyl-3,4-methylenedioxyamphetamine Benzazepines Phosphopyruvate hydratase Brain-derived neurotrophic factor Rna, messenger Dopamine antagonists Hallucinogens Microdialysis Behavioral symptoms Conditioning, operant Gene expression regulation Locomotion Male Drug dependence 3,4-Methylenedioxymethamphetamine MDMA |
| Key points | The authors report that MDMA increases BDNF expression in several brain regions and that heterozygous BDNF deletion reduces MDMA-induced place preference, behavioral sensitization, and nucleus accumbens serotonin and dopamine increases. They suggest BDNF is implicated in MDMA-induced dependence and psychosis by activating midbrain serotonergic and dopaminergic neurons. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 15
- Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2020
- 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & Behavior February 1, 2019
- Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction. Journal of Neuroscience Research April 1, 2022
- MDMA-assisted psychotherapy for PTSD: Growing evidence for memory effects mediating treatment efficacy. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2024
- [Neurotrophic mechanisms of psychedelic therapy]. Biologie aujourd'hui 2019
and 10 more in the library
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and 9 more in the library