Local and downstream effects of excitotoxic lesions in the rat medial prefrontal cortex on In vivo 1H-MRS signals.
The rat medial prefrontal cortex (mPFC) regulates subcortical dopamine transmission via projections to the striatum and ventral tegmental area. We used in vivo proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T to determine whether excitotoxic lesions of the mPFC result in alterations of N-acetylaspartate (NAA), a marker of neuronal integrity, both locally and downstream in the striatum. Lesioned rats exhibited persistent reductions of NAA and other metabolites within the prefrontal cortex; selective reductions of NAA were seen in the striatum, but not in the parietal cortex. Consistent with earlier reports, lesioned rats exhibited a transient enhancement in amphetamine-induced hyperlocomotion. Prefrontal NAA losses correlated with lesion extent. In the striatum, while there was no change in tissue volume, expression of striatal glutamic acid decarboxylase-67 mRNA was significantly reduced. In vivo NAA levels thus appear sensitive to both local and downstream alterations in neuronal integrity, and may signal meaningful effects at cellular and behavioral levels.
Roffman
J L
JL
Clinical Brain Disorders Branch, NIMH, National Institutes of Health, Bethesda, MD 20892-1379, USA.
Lipska
B K
BK
Bertolino
A
A
Van Gelderen
P
P
Olson
A W
AW
Khaing
Z Z
ZZ
Weinberger
D R
DR
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology; D003714:Denervation; D015259:Dopamine Agents / Q000494:pharmacology; D004525:Efferent Pathways / Q000378:metabolism* / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D017403:In Situ Hybridization; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015259:Dopamine Agents; D009498:Neurotoxins; D012333:RNA, Messenger; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D000661:Amphetamine; D005968:Glutamate Decarboxylase