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http://hdl.handle.net/2445/162419
Title: | Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine. |
Author: | López Arnau, Raúl Duart Castells, Leticia Aster, Barbara Camarasa García, Jordi Escubedo Rafa, Elena Pubill Sánchez, David |
Keywords: | Farmacologia Biosíntesi Farmacocinètica Cocaïna Metabolisme Drogues Estimulants Fisiologia Rates Dopamina Pharmacology Biosynthesis Pharmacokinetics Cocaine Metabolism Drugs of abuse Stimulants Physiology Rats Dopamine |
Issue Date: | 4-Oct-2018 |
Publisher: | Springer Verlag |
Abstract: | RATIONALE: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone present in bath salts. It is a powerful psychostimulant and blocker of the dopamine transporter (DAT), like cocaine. It is known that acute exposure to psychostimulants induces rapid changes in DAT function. OBJECTIVES: To investigate the effects of MDPV on DAT function comparing with cocaine. METHODS: Binding of [3H]WIN 35428 was performed on PC 12 cells treated with MDPV and washed. Rat striatal synaptosomes were incubated with MDPV or cocaine (1 μM) for 1 h and [3H]dopamine (DA) uptake was performed. Also, different treatments with MDPV or cocaine were performed in Sprague-Dawley rats to assess locomotor activity and ex vivo [3H]DA uptake. RESULTS: MDPV increased surface [3H]WIN 35428 binding on PC 12 cells. In vitro incubation of synaptosomes with MDPV produced significant increases in Vmax and KM for [3H]DA uptake. In synaptosomes from MDPV- (1.5 mg/kg, s.c.) and cocaine- (30 mg/kg, i.p.) treated rats, there was a significantly higher and more persistent increase in [3H]DA uptake in the case of MDPV than cocaine. Repeated doses of MDPV developed tolerance to this DAT upregulation and 24 h after the 5-day treatment with MDPV, [3H]DA uptake was reduced. However, a challenge with the same drugs after withdrawal recovered the DAT upregulation by both drugs and showed an increased response to MDPV vs the first dose. At the same time, animals were sensitized to the stereotypies induced by both psychostimulants. CONCLUSIONS: MDPV induces a rapid and reversible functional upregulation of DAT more powerfully and lasting than cocaine. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1007/s00213-018-5052-z |
It is part of: | Psychopharmacology, 2018, vol. 236, num. 3, p. 925-938 |
URI: | http://hdl.handle.net/2445/162419 |
Related resource: | https://doi.org/10.1007/s00213-018-5052-z |
ISSN: | 0033-3158 |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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