کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6273161 | 1614791 | 2015 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Regulation of c-fos expression by the dopamine D1-D2 receptor heteromer Regulation of c-fos expression by the dopamine D1-D2 receptor heteromer](/preview/png/6273161.png)
- Dopamine D1-D2 heteromer activation induces c-fos in the nucleus accumbens.
- A selective antagonist of the D1-D2 heteromer is the TAT-D1 peptide.
- TAT-D1 increases c-fos in cortical subregions such as prefrontal cortex.
- TAT-D1 increases c-fos expression in lateral habenula and thalamus.
The dopamine D1 and D2 receptors form the D1-D2 receptor heteromer in a subset of neurons and couple to the Gq protein to regulate intracellular calcium signaling. In the present study the effect of D1-D2 heteromer activation and disruption on neuronal activation in the rat brain was mapped. This was accomplished using the dopamine agonist SKF 83959 to activate the D1-D2 heteromer in combination with a TAT-D1 disrupting peptide we developed, and which has been shown to disrupt the D1/D2 receptor interaction and antagonize D1-D2 heteromer-induced cell signaling and behavior. Acute SKF 83959 administration to rats induced significant c-fos expression in the nucleus accumbens that was significantly inhibited by TAT-D1 pretreatment. No effects of SKF 83959 were seen in caudate putamen. D1-D2 heteromer disruption by TAT-D1 did not have any effects in any striatal subregions, but induced significant c-fos immunoreactivity in a number of cortical regions including the orbitofrontal cortex, prelimbic and infralimbic cortices and piriform cortex. The induction of c-fos by TAT-D1 was also evident in the anterior olfactory nucleus, as well as the lateral habenula and thalamic nuclei. These findings show for the first time that the D1-D2 heteromer can differentially regulate c-fos expression in a region-dependent manner either through its activation or through tonic inhibition of neuronal activity.
Journal: Neuroscience - Volume 285, 29 January 2015, Pages 194-203