The ventral tegmental area (VTA) receives CRF inputs from a number of sources including the limbic forebrain and the paraventricular nucleus of the hypothalamus (Rodaros et al. 2007). These CRF inputs form symmetric and asymmetric synapses, mostly onto dendrites that co-release either GABA or glutamate, respectively (Tagliaferro and Morales 2008). VTA dopamine neurons express both types of CRF receptors, CRF1R and CRF2R (Ungless et al. 2003), and approximately 25% of VTA dopamine neurons express the CRF binding protein (CRF-BP) (Wang et al. 2005; Wang and Morales 2008). CRF regulates dopamine neurons through a subtle interplay of effects at CRF1R, CRF2R, and CRF-BP. CRF increases the action potential firing rate in VTA dopamine neurons via CRF1R and involves a PKC-dependent enhancement of Ih (a hyperpolarization-activated inward current) (Wanat et al. 2008). CRF enhanced the amplitude and slowed the kinetics of IPSCs following activation of D2-dopamine and GABAB receptors. This action is postsynaptic and dependent on the CRF1R. The enhancement induced by CRF was attenuated by repeated in vivo exposures to psychostimulants or restraint stress (Beckstead et al. 2009).
