Abstract
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.
Highlights
Introduction to the CentrallyProjecting Edinger-Westphal NucleusSince the mid-nineteenth century, the Edinger–Westphal nucleus (EW) has been traditionally described as a parasympathetic nucleus involved in oculomotor adaptation
Using fluorescent in-situ hybridization, this study found that most of the CCK-positive neurons they examined expressed Slc17a6, indicating that they are glutamatergic, and may release glutamate in the pre-optic area (POA)
Accumulating evidence indicates that the EWcp is a complex brain region consisting of several populations of neurons with distinct neurochemistry and function
Summary
Since the mid-nineteenth century, the Edinger–Westphal nucleus (EW) has been traditionally described as a parasympathetic nucleus involved in oculomotor adaptation. Recent findings demonstrating that the EW projects centrally to other brain areas (see section below), and the lack of colocalization with markers of parasympathetic neurons and/or ciliary ganglion afferents [3,4,5,6]. Researchers distinguish at least two major subpopulations of neurons within the EW: the centrally projecting EW (EWcp) and the preganglionic EW (EWpg). Consistent with its nomenclature, the EWcp projects to numerous regions of the CNS (see Projections of the EWcp, below). Numerous studies have provided extensive evidence for the involvement of these neuropeptides, as well as the EWcp in the actions of alcohol and other drugs of abuse, which are discussed below. Brain Sci. 2020, 10, 67; doi:10.3390/brainsci10020067 www.mdpi.com/journal/brainsci
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