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• W2146291241 endingPage "2170" @default.
• W2146291241 startingPage "2157" @default.
• W2146291241 abstract "Stress induces the release of the peptide corticotropin-releasing factor (CRF) into the ventral tegmental area (VTA), and also increases dopamine levels in brain regions receiving dense VTA input. Therefore, stress may activate the mesolimbic dopamine system in part through the actions of CRF in the VTA. Here, we explored the mechanism by which CRF affects VTA dopamine neuron firing. Using patch-clamp recordings from brain slices we first determined that the presence of I(h) is an excellent predictor of dopamine content in mice. We next showed that CRF dose-dependently increased VTA dopamine neuron firing, which was prevented by antagonism of the CRF receptor-1 (CRF-R1), and was mimicked by CRF-R1 agonists. Inhibition of the phospholipase C (PLC)-protein kinase C (PKC) signalling pathway, but not the cAMP-protein kinase A (PKA) signalling pathway, prevented the increase in dopamine neuron firing by CRF. Furthermore, the effect of CRF on VTA dopamine neurons was not attenuated by blockade of I(A), I(K(Ca)) or I(Kir), but was completely eliminated by inhibition of I(h). Although cAMP-dependent modulation of I(h) through changes in the voltage dependence of activation is well established, we surprisingly found that CRF, through a PKC-dependent mechanism, enhanced I(h) independent of changes in the voltage dependence of activation. Thus, our results demonstrated that CRF acted on the CRF-R1 to stimulate the PLC-PKC signalling pathway, which in turn enhanced I(h) to increase VTA dopamine neuron firing. These findings provide a cellular mechanism of the interaction between CRF and dopamine, which can be involved in promoting the avoidance of threatening stimuli, the pursuit of appetitive behaviours, as well as various psychiatric conditions." @default.
• W2146291241 created "2016-06-24" @default.
• W2146291241 creator A5024170319 @default.
• W2146291241 creator A5045219347 @default.
• W2146291241 creator A5047309828 @default.
• W2146291241 creator A5084996975 @default.
• W2146291241 creator A5085146649 @default.
• W2146291241 date "2008-04-14" @default.
• W2146291241 modified "2023-10-16" @default.
• W2146291241 title "Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of<i>I</i>_h" @default.
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• W2146291241 doi "https://doi.org/10.1113/jphysiol.2007.150078" @default.
• W2146291241 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2465205" @default.
• W2146291241 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18308824" @default.
• W2146291241 hasPublicationYear "2008" @default.
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