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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.

Extrapyramidal symptoms may appear in Alzheimer's disease (AD). In the present study, using morphometric immunohistochemistry in 34 cases with AD-related pathology, we evaluated whether nigral burden of tau pathology or striatal burden of amyloid-β deposition correlates with dopamine transporter (DAT) expression in the striatum. Our observations show a lack of correlation between these variables and support the notion that lower striatal DAT expression in AD patients suggests concomitant nigral α-synuclein pathology. Extrapyramidal symptoms may have a complex background in AD.

Previous studies showed the reduction of dopamine transporter immunoreactivity (DAT-IR) in peripheral blood lymphocytes (PBL) in Parkinson's disease. Here we report the reduction of DAT-IR in PBL in the extrapyramidal variant of multiple system atrophy. These results suggest the reduction of DAT-IR in PBL in a variety of neurodegenerative disorders, provided the presence of damage of the central dopaminergic systems. The reduction of DAT-IR in PBL in these disorders may represent a compensatory phenomenon aimed at reducing intracellular dopamine influx and, consequently, dopamine-mediated aggravation of oxidative stress in these cells.

Rationale and Objectives: Many studies have examined the effect of experimenter-delivered methamphetamine on the mesolimbic and nigrostriatal dopamine pathways. In contrast, little is known about the effect of methamphetamine self-administration on these neuronal pathways. We studied the effect of methamphetamine self-administration on two key regulators of dopamine transmission, tyrosine hydroxylase (TH), and dopamine transporter (DAT), in components of the mesolimbic and nigrostriatal dopamine pathways., Methods: Rats self-administered methamphetamine (0.1 mg/kg per infusion, fixed-ratio-1 reinforcement schedule) or saline (control condition) for 9 h/day over 10 days. The brains of these rats were collected after 1 or 30 days of forced abstinence and the expression levels of TH and DAT were assayed by in situ, hybridization and western blot., Results: TH mRNA and protein levels were increased in the ventral tegmental area (VTA, the cell body region of the mesolimbic dopamine system) and the substantia nigra pars compacta (SNC, the cell body region of the nigrostriatal dopamine system) after 1 day, but not 30 days, of forced abstinence from methamphetamine. In contrast, methamphetamine self-administration had no effect on TH protein levels in dopaminergic terminals located in the nucleus accumbens and caudate-putamen. In addition, methamphetamine self-administration had no effect on DAT mRNA levels in the VTA., Conclusions: Results suggest that extended daily access to self-administered methamphetamine results in a transient, short-lasting effect on mesolimbic and nigrostriatal dopamine neurons of the rat brain.