Fig. 1.

Basic neurocircuitry of stressor-induced reinstatement. Stressor-induced reinstatement requires corticotropin-releasing factor (CRF), via activation of CRFR1, and noradrenergic signaling, via activation of β2-adrenergic receptors, in the bed nucleus of the stria terminalis (BNST). CRF in the BNST may arise from the local release of CRF or CRF-containing afferent projections from the central nucleus of the amygdala (CeA). The BNST then sends CRF-containing efferent projections to the ventral tegmental area (VTA) where activation of CRFR1 is critical for stressor-induced reinstatement. The VTA is further regulated by afferent GABAergic projections from the nucleus accumbens (NAc) shell and sends important dopaminergic projections to the medial prefrontal cortex (mPFC). The mPFC then sends a glutamatergic projection to the nucleus accumbens core that is necessary for stressor-, drug-, and drug-associated cue-induced reinstatement.