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2019-02-05

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cc-by-nc-nd (c) Elsevier B.V., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/130480

7,8-Dihydroxyflavone blocks the development of behavioral sensitization to MDPV, but not to cocaine: Differential role of the BDNF-TrkB pathway

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https://doi.org/10.1016/j.bcp.2019.02.004

Resum

3,4-Methylenedioxypyrovalerone (MDPV) acts as a dopamine transporter blocker and exerts powerful psychostimulant effects. In this study we aimed to investigate the bidirectional cross-sensitization between MDPV and cocaine, as well as to evaluate the role of the BDNF-TrkB signaling pathway in the development of locomotor sensitization to both drugs. Mice were treated with MDPV (1.5 mg/kg) or cocaine (10 or 15 mg/kg) once daily for 5 days. After withdrawal (10 days), animals were challenged with cocaine (8 mg/kg) or MDPV (1 mg/kg). For biochemical determinations, MDPV (1.5 mg/kg) or cocaine (15 mg/kg) were administered acutely or repeatedly, and BDNF, D3R and G9a transcription levels as well as pro- and mature BDNF protein levels were determined. Our results demonstrate that repeated administration of MDPV or cocaine sensitizes to cocaine and MDPV locomotor effects. After an acute or a repeated exposure to MDPV, cortical mRNA BDNF levels were increased, while a decrease in mBDNF protein levels in the nucleus accumbens 2 h after repeated exposure was evidenced. Interestingly, such decline was involved in the development of locomotor sensitization, thus the pretreatment with 7,8-dihydroxyflavone (10 mg/kg), a TrkB agonist, blocked the development of sensitization to MDPV but not to cocaine, for which no changes in the BDNF-TrkB signaling pathway were observed at early withdrawal. In conclusion, a bidirectional cross-sensitization between MDPV and cocaine was evidenced. Our findings suggest that decreased BDNF-TrkB signaling has an important role in the behavioral sensitization to MDPV, pointing TrkB modulation as a target to prevent MDPV sensitization Keywords: MDPV, Cocaine, Sensitization, BDNF, 7,8-Dihydroxyflavone

Matèries

Dopamina, Cocaïna, Neurofarmacologia

Matèries (anglès)

Dopamine, Cocaine, Neuropharmacology

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

Citació

DUART CASTELLS, Leticia, et al. 7,8-Dihydroxyflavone blocks the development of behavioral sensitization to
MDPV, but not to cocaine: Differential role of the BDNF-TrkB pathway. Biochemical Pharmacology. 2019. Vol. 163, num. 84-93. ISSN 0006-2952. [consulted: 4 of August of 2026]. Available at: https://hdl.handle.net/2445/130480

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