[Abstract Title]. - Society for Neuroscience

Poster
274. Basal Ganglia: Transmitters and Neuromodulation II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 274.14/JJ9
Topic: D.15.a. Transmitters and neuromodulation
Support: AG 21937
Title: Rat strain affects sensitivity of striatal dopamine and glutamate synapses to 3-NP toxicity
Authors: *J. P. WALSH 1 , G. AKOPIAN 2 , M. CAPPELLETTI 2 , M. JAKOWEC 3 , G.
PETZINGER 3 , C. CRAWFORD 4 ;
1 Dept Gerontol, Univ. So California, Los Angeles, CA; 2 Gerontology & Neurosci., 3 Neurol.,
USC, Los Angeles, CA; 4 Psychology, California State University, San Bernardino, San
Bernardino, CA
Abstract: The striatum is particularly sensitive to the irreversible inhibitor of succinate
dehyrdrogenase 3-nitropropionic acid (3-NP). In the present study we examined early changes in
behavior, dopamine and glutamate synaptic physiology created by a single systemic injection of
3-NP in Fischer 344 rats. Hind limb dystonia was seen 2 hours after 3-NP injections and rats
performed poorly on balance beam and rota-rod motor tests 24 hours later, with improvement by
48 hours. Systemic 3-NP caused a similar temporal pattern for increased expression of a NMDA
receptor-dependent form of long-term potentiation (LTP) at corticostriatal synapses. The 3-NP
induced corticostriatal LTP was not due to increased NMDA receptor number or function, since
3-NP did not change MK-801 binding and NMDA/AMPA receptor current ratios. The LTP seen
24 hours after 3-NP was D1 receptor-dependent and reversed by exogenous addition of
dopamine or a D2 receptor agonist to brain slices. High performance liquid chromatography and
fast scan cyclic voltammetry revealed a decrease in dopamine content and release in rats injected
24 hours earlier with 3-NP, and much like the enhanced LTP, dopamine changes were reversed
by 48 hours. Tyrosine hydroxylase expression was not changed and there was no evidence of
striatal cell loss at 24-48 hours after 3-NP exposure. Sprague-Dawley rats showed similar
physiological responses to systemic 3-NP, albeit with reduced sensitivity. Thus, 3-NP causes
significant changes in motor behavior marked by parallel changes in striatal dopamine release
and corticostriatal synaptic plasticity.
Disclosures: J.P. Walsh , This research was supported by a grant from the NIH (AG 21937),
B. Research Grant (principal investigator, collaborator or consultant and pending grants as well
as grants already received); G. Akopian, None; M. Jakowec, None; G. Petzinger, None; C.
Crawford, None; M. Cappelletti, None.