Effects of prefrontal cortical lesions on neuropeptide and dopamine receptor gene expression in the striatum-accumbens complex.
In the rat, neurochemical, behavioral, and anatomical investigations suggest that medial prefrontal cortical input modulates the activity of the basal ganglia. To understand how prefrontal dysfunction might alter striatal-accumbens function, in situ hybridization histochemistry with S35-labeled oligonucleotide probes was used to assess changes in striatal-accumbens gene expression following bilateral excitotoxic ibotenic acid (IA) lesions of the rat medial prefrontal cortex. Quantitative densitometry was used to measure changes in mRNA levels for preproenkephalin A (ENK), D1 dopamine receptor, protachykinin (SubP), glutamic acid decarboxylase (GAD65), and D2 dopamine receptor. No differences were found between sham and lesion groups for ENK, D1, SubP, or GAD65 mRNA levels in the striatum or nucleus accumbens (NAC). D2 receptor mRNA levels were, however, significantly higher in the dorsomedial striatum and in the core area of the NAC of the lesioned rats. Although the functional significance of increased D2 mRNA is unclear, these findings demonstrate that glutamate mPFC projections modulate gene expression in relatively regionally-localized subcortical neuronal populations.
Baca
S M
SM
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Neuroscience Center, St. Elizabeths Hospital, Washington, DC 20032, USA.
Lipska
B K
BK
Egan
M F
MF
Bachus
S E
SE
Ferguson
J N
JN
Hyde
T M
TM
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000737:chemistry* / Q000201:enzymology; D004745:Enkephalins / Q000235:genetics; D018690:Excitatory Amino Acid Agonists; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000235:genetics; D007051:Ibotenic Acid; D008297:Male; D009479:Neuropeptides / Q000235:genetics; D009714:Nucleus Accumbens / Q000737:chemistry* / Q000201:enzymology; D017397:Prefrontal Cortex / Q000737:chemistry* / Q000201:enzymology; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics
D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015320:Tachykinins; C054618:protachykinin; D007051:Ibotenic Acid; C033660:preproenkephalin; D005968:Glutamate Decarboxylase