Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine

• Published in: Psychopharmacology 2019-03, Vol.236 (3), p.925-938
• Main Authors: Lopez-Arnau, Raul, Duart-Castells, Leticia, Aster, Barbara, Camarasa, Jorge, Escubedo, Elena, Pubill, David
• Format: Article
• Language: English
• Subjects: Bath products; Biomedical and Life Sciences; Biomedicine; Cocaine; Dopamine; Dopamine transporter; Drug abuse; Incubation; Locomotor activity; Neostriatum; Neurosciences; Original Investigation; Personal computers; Pharmacology/Toxicology; Phenols (Class of compounds); Psychiatry; Rats; Resveratrol; Rodents; Salts; Synaptosomes; Withdrawal
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-5052-z

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 [ 3 H]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 [ 3 H]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 [ 3 H]DA uptake. Results MDPV increased surface [ 3 H]WIN 35428 binding on PC 12 cells. In vitro incubation of synaptosomes with MDPV produced significant increases in V max and K M for [ 3 H]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 [ 3 H]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, [ 3 H]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.