We combined in vitro amperometric, optical analysis of fluorescent false neurotransmitters and microdialysis techniques to unveil that cocaine and methylphenidate induced a marked depression of the synaptic release of dopamine (DA) in mouse striatum. In contrast to the classical dopamine transporter (DAT)-dependent enhancement of the dopaminergic signal observed at concentrations of cocaine lower than 3 μM, the inhibitory effect of cocaine was found at concentrations higher than 3 μM. The paradoxical inhibitory effect of cocaine and methylphenidate was associated with a decrease in synapsin phosphorylation. Interestingly, a cocaine-induced depression of DA release was only present in cocaine-insensitive animals (DAT-CI). Similar effects of cocaine were produced by methylphenidate in both wild-type and DAT-CI mice. On the other hand, nomifensine only enhanced the dopaminergic signal either in wild-type or in DAT-CI mice. Overall, these results indicate that cocaine and methylphenidate can increase or decrease DA neurotransmission by blocking reuptake and reducing the exocytotic release, respectively. The biphasic reshaping of DA neurotransmission could contribute to different behavioral effects of psychostimulants, including the calming ones, in attention deficit hyperactivity disorder.

Federici, M., Latagliata, E., Ledonne, A., Rizzo, F., Feligioni, M., Sulzer, D., et al. (2014). Paradoxical abatement of striatal dopaminergic transmission by cocaine and methylphenidate. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 289(1), 264-274 [10.1074/jbc.M113.495499].

Paradoxical abatement of striatal dopaminergic transmission by cocaine and methylphenidate

NISTICO', ROBERT GIOVANNI;MERCURI, NICOLA BIAGIO
2014-01-03

Abstract

We combined in vitro amperometric, optical analysis of fluorescent false neurotransmitters and microdialysis techniques to unveil that cocaine and methylphenidate induced a marked depression of the synaptic release of dopamine (DA) in mouse striatum. In contrast to the classical dopamine transporter (DAT)-dependent enhancement of the dopaminergic signal observed at concentrations of cocaine lower than 3 μM, the inhibitory effect of cocaine was found at concentrations higher than 3 μM. The paradoxical inhibitory effect of cocaine and methylphenidate was associated with a decrease in synapsin phosphorylation. Interestingly, a cocaine-induced depression of DA release was only present in cocaine-insensitive animals (DAT-CI). Similar effects of cocaine were produced by methylphenidate in both wild-type and DAT-CI mice. On the other hand, nomifensine only enhanced the dopaminergic signal either in wild-type or in DAT-CI mice. Overall, these results indicate that cocaine and methylphenidate can increase or decrease DA neurotransmission by blocking reuptake and reducing the exocytotic release, respectively. The biphasic reshaping of DA neurotransmission could contribute to different behavioral effects of psychostimulants, including the calming ones, in attention deficit hyperactivity disorder.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14
English
Con Impact Factor ISI
Dopamine Uptake Inhibitors; Animals; Amperometry; Dopamine Transporters; Corpus Striatum; Exocytosis; Methylphenidate; Mice; Electrophysiology; Synapsins; Drug Action; Microdialysis; Dopamine; Phosphorylation; Transgenic Mice; Cocaine; Striatum; Synaptic Transmission
Federici, M., Latagliata, E., Ledonne, A., Rizzo, F., Feligioni, M., Sulzer, D., et al. (2014). Paradoxical abatement of striatal dopaminergic transmission by cocaine and methylphenidate. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 289(1), 264-274 [10.1074/jbc.M113.495499].
Federici, M; Latagliata, E; Ledonne, A; Rizzo, F; Feligioni, M; Sulzer, D; Dunn, M; Sames, D; Gu, H; Nistico', Rg; Puglisi Allegra, S; Mercuri, Nb
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/100971
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