Glutamate decarboxylase (GAD65) gene expression is increased by dopamine receptor agonists in a subpopulation of rat striatal neurons.
The mRNA levels encoding for the two isoforms of glutamate decarboxylase (GAD65 and GAD67) were measured in the adult rat striatum following systemic administration of dopamine receptor agonists. Double-labeling in situ hybridization histochemistry was used to measure GAD65 or GAD67 mRNA levels in neurons labeled or not with a preproenkephalin (PPE) cRNA probe. Chronic treatment with the D1/D2 dopamine receptor agonist apomorphine or with the D1 dopamine receptor agonist SKF-38393 induced an increase in GAD65 but not GAD67 mRNA levels in different sectors of the striatum. These effects were abolished by pre-administration of the D1 dopamine receptor antagonist SCH-23390. On double-labeled sections, GAD65 mRNA labeling was distributed in neurons labeled and unlabeled with the PPE cRNA probe. About half of all neuronal profiles labeled with the GAD65 cRNA probe were also labeled with the PPE cRNA probe. Quantification of labeling at cellular level demonstrated a significant increase of GAD65 mRNA levels in PPE-unlabeled neurons. On the other hand, no significant changes of GAD65 mRNA levels were detected in PPE-labeled neurons. Our results demonstrate a differential effect of dopamine receptor agonists on striatal GAD65 and GAD67 gene expression. In particular, we show that GAD65 mRNA levels are selectively increased in presumed striato-nigral neurons following treatments with dopamine receptor agonists. These data provide evidence that the GAD65 isoform is preferentially involved in the regulation of GABAergic neurotransmission in striato-nigral neurons.
Laprade
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Centre de Recherche en Neurobiologie, Université Laval, Québec, Canada.
Soghomonian
J J
JJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000235:genetics*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018075:RNA, Complementary; D051381:Rats; D017207:Rats, Sprague-Dawley
D018491:Dopamine Agonists; D018075:RNA, Complementary; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D005968:Glutamate Decarboxylase; D001058:Apomorphine