The PKC inhibitor Ro31-8220 blocks acute amphetamine-induced dopamine overflow in the nucleus accumbens

Jessica A. Loweth, Robyn Svoboda, Jennifer D. Austin, Anitra M. Guillory, Paul Vezina

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Acute administration of the psychostimulant amphetamine increases extracellular levels of dopamine (DA) by reversing the DA transporter on ascending midbrain DA neurons. In vitro studies using striatal synaptosomal, slice and nucleus accumbens (NAcc) tissue preparations have implicated protein kinase C (PKC) in this effect. The present study further examined this effect in vivo by assessing the ability of the PKC inhibitor, Ro31-8220 (10 μM), to inhibit acute amphetamine-induced DA overflow when applied with this drug to the NAcc via reverse dialysis. Amphetamine was applied at a concentration of 30 μM, and the core and shell subregions of the NAcc were assayed separately in freely moving rats. These brain regions play a role in the acute locomotor-activating and motivational effects of amphetamine. Consistent with the findings of previous in vitro experiments, reverse dialysis of Ro31-8220 with amphetamine robustly attenuated the ability of this drug to increase extracellular levels of dopamine in both the core and shell subregions of the NAcc. These results confirm that amphetamine stimulates dopamine overflow via a PKC-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)88-92
Number of pages5
JournalNeuroscience Letters
Volume455
Issue number2
DOIs
StatePublished - May 15 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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