BRIEF MITOCHONDRIAL INHIBITION CAUSES LASTING CHANGES IN MOTOR BEHAVIOR AND CORTICOSTRIATAL SYNAPTIC PHYSIOLOGY IN THE FISCHER 344 RAT

作者：Akopian G; Crawford C; Petzinger G; Jakowec M W; Walsh J P^*

来源：Neuroscience, 2012, 215: 149-159.

DOI：10.1016/j.neuroscience.2012.04.060

• dopamine
• striatum
• 3-NP
• LTD
• LTP

The striatum is particularly vulnerable to mitochondrial dysfunction and this problem is linked to pathology created by environmental neurotoxins, stimulants like amphetamine, and metabolic disease and ischemia. We studied the course of recovery following a single systemic injection of the mitochondria! complex II inhibitor 3-nitropropionic acid (3-NP) and found 3-NP caused lasting changes in motor behavior that were associated with altered activity-dependent plasticity at corticostriatal synapses in Fischer 344 rats. The changes in synapse behavior varied with the time after exposure to the 3-NP injection. The earliest time point studied, 24 h after 3-NP, revealed 3-NP-induced an exaggeration of D1 Dopamine (DA) receptor dependent long-term potentiation (LTP) that reversed to normal by 48 h post-3-NP exposure. Thereafter, the likelihood and degree of inducing D2 DA receptor dependent long-term depression (LTD) gradually increased, relative to saline controls, peaking at 1 month after the 3-NP exposure. NMDA receptor binding did not change over the same post 3-NP time points. These data indicate even brief exposure to 3-NP can have lasting behavioral effects mediated by changes in the way DA and glutamate synapses interact.

• 出版日期2012-7-26