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A substrate trapping mutant form of striatal-enriched protein tyrosine phosphatase prevents amphetamine-induced stereotypies and long-term potentiation in the striatum.

Authors: Tashev, R  Moura, PJ  Venkitaramani, DV  Prosperetti, C  Centonze, D  Paul, S  Lombroso, PJ 
Citation: Tashev R, etal., Biol Psychiatry. 2009 Apr 15;65(8):637-45. doi: 10.1016/j.biopsych.2008.10.008. Epub 2008 Nov 20.
Pubmed: (View Article at PubMed) PMID:19026408
DOI: Full-text: DOI:10.1016/j.biopsych.2008.10.008

BACKGROUND: Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. METHODS: A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and 1 hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. RESULTS: Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. CONCLUSIONS: A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

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CRRD Object Information
CRRD ID: 9835020
Created: 2015-03-13
Species: All species
Last Modified: 2015-03-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.