Elsevier

Molecular Brain Research

Volume 34, Issue 1, 1 December 1995, Pages 65-74
Molecular Brain Research

Research report
Differential regulation of mRNA levels encoding for the two isoforms of glutamate decarboxylase (GAD65 and GAD67) by dopamine receptors in the rat striatum

https://doi.org/10.1016/0169-328X(95)00139-JGet rights and content

Abstract

The effects of in vivo administration of dopamine receptor agonists on the mRNA levels encoding for the two isoforms of glutamate decarboxylase, GAD65 and GAD67, and for preproenkephalin were studied in regions of the rat dorsal striatum by radioactive in situ hybridization histochemistry. Changes in striatal mRNA levels after drug treatment were quantified by computerized densitometry on X-ray films. Chronic administration of the dopamine receptor agonist apomorphine or the D1 dopamine receptor agonist SKF-38393 resulted in increased GAD65 mRNA levels in the dorsomedial, ventromedial, dorsolateral and ventrolateral sectors of the striatum. Apomorphine or SKF-38393 treatment did not induce significant effects on GAD67 and preproenkephalin mRNA levels in striatum. On the other hand, chronic administration of the D2 dopamine receptor agonist quinpirole significantly decreased GAD67 in the dorsolateral and ventrolateral and preproenkephalin in the ventrolateral sectors of the striatum. Quinpirole treatment did not induce significant changes in GAD65 mRNA levels. Chronic administration of the dopamine receptor antagonist haloperidol resulted in a significant increase in GAD67 and preproenkephalin mRNA levels in the dorsomedial, dorsolateral and ventrolateral striatal sectors. Chronic treatment with the D2/D3 dopamine receptor antagonist sulpiride resulted in a significant increase in GAD67 in the ventromedial and ventrolateral and PPE in the dorsomedial and ventrolateral striatal sectors. Haloperidol or sulpiride did not induce significant changes in striatal GAD65 mRNA levels. Chronic administration of the D1 dopamine receptor antagonist SCH-23390 had nod significant effect on GAD67, GAD65 or preproenkephalin mRNA levels. In the present experimental conditions, stimulation of dopamine receptors with apomorphine or SKF-38393 resulted in increased GAD65 mRNA levels whereas blockade of dopamine receptors with haloperidol or sulpiride resulted in increased GAD67 mRNA levels. These results indicate that striatal GAD65 and GAD67 mRNA levels are differentially regulated by dopamine receptor subtypes.

References (50)

  • M. Jaber et al.

    Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary

    Mol. Brain Res.

    (1994)
  • H.K. Jiang et al.

    Differential modulation of striatonigral dynorphin and enkephalin by dopamine receptor subtypes

    Brain Res.

    (1990)
  • B.J. Morris et al.

    Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: contrasting effects of D1 and D2 antagonists

    Neuroscience

    (1988)
  • E. Normand et al.

    Anatomical study of enkephalin gene expression in the rat forebrain following haloperidol treatment

    Neurosci. Lett.

    (1987)
  • S. Pedneault et al.

    Glutamate decarboxylase (GAD65) mRNA levels in the striatum and pallidum of MPTP-treated monkeys

    Mol. Brain Res.

    (1994)
  • Z.H. Qin et al.

    Dopaminergic and glutamatergic blocking drugs differentially regulate glutamic acid decarboxylase mRNA in mouse brain

    Mol. Brain Res.

    (1994)
  • M.S. Reid et al.

    The effects of intranigral GABA and dynorphin A injections on striatal dopamine and GABA release: evidence that dopamine provides inhibitory regulation of striatal GABA neurons via D2 receptors

    Brain Res.

    (1990)
  • A. Reiner et al.

    The patterns of neurotransmitter and neuropeptide co-occurrence among striatal projection neurons: conclusions based on recent findings

    Brain Res. Rev.

    (1990)
  • G.J. Romano et al.

    Haloperidol increases proenkephalin mRNA levels in the caudate-putamen of the rat: a quantitative study at the cellular level using in situ hybridization

    Mol. Brain Res.

    (1987)
  • J. Segovia et al.

    Parallel increase in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway

    Brain Res.

    (1990)
  • J.-J. Soghomonian

    Differential regulation of glutamate decarboxylase and preproenkephalin mRNA levels in the rat striatum

    Brain Res.

    (1994)
  • J.-J. Soghomonian et al.

    Messenger RNAs encoding glutamate-decarboxylase are differentially affected by nigrostriatal lesions in subpopulations of striatal neurons

    Brain Res.

    (1992)
  • K. Yoshikawa et al.

    Rat brain preproenkephalin mRNA

    J. Biol. Chem.

    (1984)
  • J.A. Angulo

    Involvement of dopamine D1 and D2 receptors in the regulation of proenkephalin mRNA abundance in the striatum and accumbens of the rat brain

    J. Neurochem.

    (1992)
  • S.J. Augood et al.

    Contrasting effects of raclopride and SCH-23390 on the cellular content of preproenkephalin A mRNA in rat striatum: a quantitative non-radioactive in situ hybridization study

    Eur. J. Neurosci.

    (1992)
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