Similar to the findings with alcohol, urocortins may also influence stimulant drug seeking and consumption through actions on systems that mediate approach behavior rather than avoidance. It is well established that mesolimbic dopamine (DA) neurons originating in the ventral tegmental area (VTA) are critical for exploration and approach behaviors (Koob and Volkow, 2010). Electrophysiological experiments on VTA slice preparations found that bath application of CRF potentiates NMDAR-mediated excitatory postsynaptic currents in DA neurons, an effect that was blocked by CRF2R but not CRF1R antagonists (Ungless et al., 2003). This finding was surprising, because mRNA for CRF2R had not been detected in the VTA by in situ hybridization (Van Pett et al., 2000). Subsequent single-cell RT-PCR data suggested that CRF2R transcript, is expressed in VTA DA neurons, although perhaps at levels too low to be detected by in situ (Ungless et al., 2003). The presence of CRF2R in the DA neurons of the VTA has remained controversial (Wise and Morales, 2010), but it has been shown that CRF2R is required for potentiation of NMDAR transmission and Ca2+ release in these cells (Riegel and Williams, 2008; Ungless et al., 2003).
