The essential role of corticotropin releasing factor (CRF) and its type-1 receptor (CRF1) in stress-induced relapse to drug seeking has been demonstrated. The bed nucleus of the stria terminalis is the major anatomical substrate for this CRF/CRF1 receptor action. More recently, the role of type-2 CRF (CRF2) receptors in stress-induced relapse to cocaine seeking has also has been documented. The ventral tegmental area is the anatomical substrate for this CRF/CRF2 receptor action. The new information involving CRF2 receptors in stress-induced relapse to cocaine seeking has generated a need for a reappraisal of the existing anatomical and pharmacological evidence that have been used to support the critical role of CRF1 receptors. The role of CRF2 receptors in stress-induced relapse to drug seeking also opens the question of the putative role of the other peptides of the CRH family (urocotin-1, urocortin-2 and urocortin-3) that have high affinity for CRF2 receptors. In this commentary, the available evidence supporting the role of both CRF1 and CRF2 receptors in stress-induced relapse to drug seeking is reviewed.
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