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Medial forebrain bundle stimulation or D-2 dopamine receptor activation increases preproenkephalin mRNA in rat
M J Bannon1, M Kelland, L A Chiodo
1Laboratory of Molecular Neurobiology, Sinai Research Institute, Detroit, Michigan.
Abstract:
Electrical stimulation of the medial forebrain bundle, in a manner that augmented the release of dopamine in the forebrain, rapidly increased the striatal content of preproenkephalin (but not preprotachykinin) mRNA. This effect was mimicked by administration of either the indirect (dopamine-releasing) agonist methamphetamine or by the D-2 dopamine receptor agonist quinpirole, but not by the D-1 agonist SKF 38393. These data suggest that D-2 receptors, which mediate a stimulatory effect on enkephalin gene expression, may be subsaturated under basal conditions and, therefore, responsive to increases in synaptic dopamine.
Insights
Electrical stimulation of the medial forebrain bundle increases dopamine release and boosts enkephalin (but not tachykinin) mRNA in the striatum. This suggests D-2 dopamine receptors regulate this gene expression response.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The medial forebrain bundle (MFB) is a key pathway for dopamine (DA) in the brain.
- Dopamine signaling is crucial for various functions, including reward and motor control.
- Enkephalin and tachykinin are neuropeptides involved in pain modulation and reward pathways.
Purpose of the Study:
- To investigate the effect of enhanced dopamine release on neuropeptide gene expression in the striatum.
- To determine the specific dopamine receptor subtypes involved in regulating enkephalin and tachykinin mRNA levels.
Main Methods:
- Electrical stimulation of the medial forebrain bundle in rodents.
- Measurement of preproenkephalin and preprotachykinin mRNA levels in the striatum.
- Administration of dopamine agonists (methamphetamine, quinpirole, SKF 38393) and assessment of downstream effects.
Main Results:
- Electrical stimulation that increased forebrain dopamine rapidly elevated striatal preproenkephalin mRNA but not preprotachykinin mRNA.
- This effect was replicated by methamphetamine (indirect DA agonist) and quinpirole (D-2 agonist) but not SKF 38393 (D-1 agonist).
- These findings indicate a selective upregulation of enkephalin gene expression mediated by D-2 dopamine receptors.
Conclusions:
- Dopamine D-2 receptors play a significant role in stimulating enkephalin gene expression.
- The D-2 receptor system may be under-stimulated under normal conditions, making it sensitive to dopamine level changes.
- This study elucidates a specific mechanism linking dopamine signaling to enkephalin production in the striatum.