Figure 4. CREB and dynorphin in the NAc in depression.

The figure shows a simplified hypothetical scheme by which CREB induction of dynorphin (DYN) in the NAc contributes to certain symptoms of depression. CREB is activated by D1 dopamine receptors (through activation of the cAMP pathway) or by Ca²⁺- or TrkB-regulated signal transduction pathways, which leads to increased expression of DYN. DYN feeds back on κ-opioid receptors located on the terminals and cell bodies/dendrites of VTA dopamine (DA) neurons. Stimulation of these κ receptors inhibits the VTA neurons, which may contribute to anhedonia and related symptoms of depression. Antagonists of κ receptors may thus block the consequences of CREB-induced increases in DYN activity, and exert antidepressant activity in some individuals. From Nestler and Carlezon (2006) with permission.