Involvement of Centrally Projecting Edinger–Westphal Nucleus Neuropeptides in Actions of Addictive Drugs

The centrally-projecting Edinger–Westphal nucleus (EWcp) is a brain region distinct from the preganglionic Edinger–Westphal nucleus (EWpg). In contrast to the EWpg, the EWcp does not send projections to the ciliary ganglion and appears not to regulate oculomotor function. Instead, evidence is accumulating that the EWcp is extremely sensitive to alcohol and several other drugs of abuse. Studies using surgical, genetic knockout, and shRNA approaches further implicate the EWcp in the regulation of alcohol sensitivity and self-administration. The EWcp is also known as the site of preferential expression of urocortin 1, a peptide of the corticotropin-releasing factor family. However, neuroanatomical data indicate that the EWcp is not a monotypic brain region and consists of several distinct subpopulations of neurons. It is most likely that these subpopulations of the EWcp are differentially involved in the regulation of actions of addictive drugs. This review summarizes and analyzes the current literature of the EWcp’s involvement in actions of drugs of abuse in male and female subjects in light of the accumulating evidence of complexities of this brain region.

Corticotropin-releasing factor receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Corticotropin-releasing factor (CRF, nomenclature as agreed by the NC-IUPHAR subcommittee on Corticotropin-releasing Factor Receptors [30]) receptors are activated by the endogenous peptides corticotrophin-releasing hormone, a 41 amino-acid peptide, urocortin 1, 40 amino-acids, urocortin 2, 38 amino-acids and urocortin 3, 38 amino-acids. CRF1 and CRF2 receptors are activated non-selectively by CRH and UCN. CRF2 receptors are selectively activated by UCN2 and UCN3. Binding to CRF receptors can be conducted using radioligands [125I]Tyr0-CRF or [125I]Tyr0-sauvagine with Kd values of 0.1-0.4 nM. CRF1 and CRF2 receptors are non-selectively antagonized by α-helical CRF, D-Phe-CRF-(12-41) and astressin. CRF1 receptors are selectively antagonized by small molecules NBI27914, R121919, antalarmin, CP 154,526, CP 376,395. CRF2 receptors are selectively antagonized by antisauvagine and astressin 2B.