Corticotropin‐releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C‐dependent enhancement ofIh

• DOI: 10.1113/jphysiol.2007.150078
• Publication Date: 2008-02-29T01:46:37Z
• Authors: M. J. Wanat; F. W. Hopf; G. D. Stuber; P. E. M. Phillips; A. Bonci
• Keywords: Neurons; Patch-Clamp Techniques; Dose-Response Relationship, Drug; Corticotropin-Releasing Hormone; Dopamine; Ventral Tegmental Area; Action Potentials; Mice, Transgenic; Membrane Potentials; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Protein Kinase C

Stress induces the release of peptide corticotropin-releasing factor (CRF) into ventral tegmental area (VTA), and also increases dopamine levels in brain regions receiving dense VTA input. Therefore, stress may activate mesolimbic system part through actions CRF VTA. Here, we explored mechanism by which affects neuron firing. Using patch-clamp recordings from slices first determined that presence I(h) is an excellent predictor content mice. We next showed dose-dependently increased firing, was prevented antagonism receptor-1 (CRF-R1), mimicked CRF-R1 agonists. Inhibition phospholipase C (PLC)-protein kinase (PKC) signalling pathway, but not cAMP-protein A (PKA) increase firing CRF. Furthermore, effect on neurons attenuated blockade I(A), I(K(Ca)) or I(Kir), completely eliminated inhibition I(h). Although cAMP-dependent modulation changes voltage dependence activation well established, surprisingly found CRF, a PKC-dependent mechanism, enhanced independent activation. Thus, our results demonstrated acted to stimulate PLC-PKC turn These findings provide cellular interaction between dopamine, can be involved promoting avoidance threatening stimuli, pursuit appetitive behaviours, as various psychiatric conditions.