The neonatal ventral hippocampal lesion model of schizophrenia: effects on dopamine and GABA mRNA markers in the rat midbrain.
The neonatal ventral hippocampal lesion in the rat has been used as a model of schizophrenia, a human disorder associated with changes in markers of dopamine and gamma-aminobutyric acid (GABA) circuits in various regions of the brain. We investigated whether alterations in mRNA markers related to the activity of midbrain dopaminergic and GABAergic neurons are associated with this model. We used in situ hybridization histochemistry to assess expression of mRNAs for dopamine transporter (DAT), tyrosine hydroxylase (TH) and glutamate decarboxylase-67 (GAD67) in the midbrain of adult rats with neonatal and adult ibotenic acid lesions of the ventral hippocampus. Neonatally lesioned rats showed in adulthood significantly reduced expression of DAT mRNA in the substantia nigra and the ventral tegmental area but no changes in the expression of TH and GAD67 mRNAs in these midbrain regions. Adult lesioned rats showed no changes in the expression of any of these genes. As the neonatal ventral hippocampal lesion reproduces many aspects of schizophrenia and is used as an animal model of this disorder, these results suggest that the reduction in DAT mRNA could result from developmental neuropathology in the ventral hippocampus and may thus represent a molecular substrate of the disease process.
Lipska
Barbara K
BK
Clinical Brain Disorders Branch, National Institute of Mental Health, Bldg.10, Rm. 4 N306, Bethesda, MD 20892-1385, USA. lipskab@intra.nimh.nih.gov
Lerman
Daniel N
DN
Khaing
Zin Z
ZZ
Weinberger
Daniel R
DR
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000293:injuries; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D017403:In Situ Hybridization / Q000379:methods; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000033:anatomy & histology / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012559:Schizophrenia / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493216:Slc6a3 protein, rat; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D004298:Dopamine