Figure 3.

Simplified depiction of the mesolimbic dopamine (DA) feedback circuit in which psychostimulants and CREB exert key effects. Psychostimulants trigger activation of CREB in the GABAergic neurons of the NAc via indirect actions on receptors (e.g., D₁, TrkB) and/or channels that gate calcium (Ca²⁺). CREB-mediated increases in dynorphin (DYN) expression reduce release of DA by acting on inhibitory κ opioid receptors (KORs) located on DA terminals in the NAc and/or VTA cell bodies. The inhibitory effect of DYN in VTA would also be expected to influence DA transmission in prefrontal cortex (PFC), amygdala (AMG), and other structures that receive projections from this region.