Stress Hormone Enhances Synaptic NMDA Response on Dopamine Neurons

belongs to a family of related peptides that includes the Urocortins. Stress potently releases CRF not only from the hypothalamus but also from extrahypothalamic neu-rons (Tsigos and Chrousos, 2002). Two genes have been Stress can induce cravings and relapse in abstinent identified in mammals that encode CRF receptors, CRF-drug addicts. In this issue of Neuron, Ungless et al. R1 and CRF-R2 (Carrasco and Van de Kar, 2003). Both report that corticotropin-releasing factor (CRF), a key of them are Gs-coupled receptors. When Ungless et al. hormone in the stress response, potentiates the applied CRF to the bath, NMDAR-mediated excitatory N-methyl-D-aspartate NMDA receptor (NMDAR) com-postsynaptic currents (EPSCs) increased, but the AMPAR ponent of glutamatergic synaptic transmission onto component of the EPSCs did not. Specific inhibition of midbrain dopamine neurons, a mechanism that may the CRF-R2 by Antisauvagine-30 inhibited CRF's po-mediate some effects of stress on relapse. in the stress response. The paraventricular nucleus of This fascinating link between a stress hormone and the hypothalamus releases corticotropin-releasing fac-excitatory transmission onto VTA DA neurons has three tor (CRF) and arginine vasopressin (AVP), which trigger unexpected mechanistic twists. First, CRF-Rs are Gs-the release of adrenocorticotrophic hormone (ACTH) coupled receptors, suggesting that the cAMP/protein from the anterior pituitary. ACTH subsequently stimu-kinase A pathway would be involved. However, inhibition lates the release of glucocorticoids from the adrenal of that pathway did not alter CRF's effect. Second, CRF-cortex (Carrasco and Van de Kar, 2003). In concert with R2 was not thought to be significantly expressed in the multiple neurotransmitter systems, these hormones pro-VTA, but a sensitive search using RT-PCR revealed its duce physical adjustments, such as increased blood presence. Finally, the most significant twist is that the pressure, increased heart rate, and inhibition of the CRF-BP seems to serve an active role in the CRF-medi-growth and reproductive systems. Likewise, there are ated process. CRF-BP binds CRF with high affinity (Car-behavioral adaptations, such as suppression of feeding rasco and Van de Kar, 2003), but understanding of its and reproduction, accompanied by increased arousal, roles is not well developed beyond its ability to serve as vigilance, and attention. a CRF buffer (Linton et al., 1990). CRF-BP participation in Stress also is an important factor in the use of ad-this synaptic process suggests it may contribute to other dictive drugs. Evidence indicates that stress can in-signals by CRF and by related peptides, such as the crease the motivation and vulnerability for …