Galanin and opioids : molecular and behavioral interactions in opioid use disorder circuits

Author/Creator:

Foster, Stephanie L., author

Publication/Creation:

Ann Arbor : ProQuest Dissertations & Theses, 2021

Resource Type:

Book

More Details

Additional/Related Title Information

Full Title:

Galanin and opioids : molecular and behavioral interactions in opioid use disorder circuits / Stephanie L. Foster

Related Names

Additional Author/Creators:

Weinshenker, David, degree supervisor
Emory University. Graduate Division of Biological and Biomedical Sciences, degree granting institution

Subjects/Genre

Genre:

Electronic dissertations
Academic theses

Description/Summary

Summary:

The neuropeptide galanin has been shown to oppose the behavioral effects of opioids, particularly withdrawal and reward. The galaninergic system has therefore been identified as a possible therapeutic target for opioid use disorder (OUD). However, most studies have utilized body- and brain-wide galanin manipulations, leaving system-specific questions about galanin - which could inform targeted therapies for OUD - largely unanswered. Given that the noradrenergic system is implicated in opioid-mediated behaviors and that its major nucleus, the locus coeruleus (LC), strongly expresses galanin, noradrenergic-derived galanin is a prime target for system-specific investigation. Additionally, the mechanisms by which galanin blocks opioid reward and withdrawal remain unclear, but current theories for both implicate galanin receptor 1 (GalR1). Previous work suggests that LC-derived galanin acts on GalR1 within the LC to suppress withdrawal symptoms. In the ventral tegmental area (VTA), GalR1 forms heteromers with the mu opioid receptor (MOR), potentially allowing galanin to directly interfere with opioid signaling and attenuate reward. Therefore, the goal of this dissertation was to examine 1) whether noradrenergic galanin modulates opioid withdrawal and reward behaviors, and 2) to evaluate whether the pattern of GalR1 expression in the LC and in reward circuits provides clues about its contribution to these two aspects of OUD. We demonstrate here that manipulating noradrenergic galanin does not affect naloxone-precipitated withdrawal symptoms. We also show, for the first time, that the distribution of GalR1 in the LC is inconsistent with previous mechanistic theories of galanin-mediated suppression of withdrawal. Regarding opioid reward and reinforcement, we find that altered noradrenergic galanin levels do not affect by acute morphine-induced locomotion, morphine conditioned place preference, or intravenous remifentanil self-administration. Characterization of GalR1 and MOR mRNA co-expression indicates that the rostromedial tegmental nucleus and the VTA, two populations that exert GABAergic control over VTA dopamine neurons, both exhibit GalR1-MOR co-expression in a quarter of GABAergic neurons. Together, these findings constitute the first system-specific investigation of galanin effects on OUD-related behaviors. This work indicates that while noradrenergic galanin does not modulate opioid withdrawal or reward behaviors, enhancing GalR1-MOR heteromeric activity in the VTA may be an important area of focus for future studies.

Language:

English

Language Note:

English

Physical Type/Description:

1 electronic resource (192 pages)

Restrictions on Access:

This item must not be sold to any third party vendors.
This item is not available from ProQuest Dissertations & Theses.

General Note:

Source of abstract: Dissertations Abstracts International, Volume: 83-04, Section: B.
Advisors: Weinshenker, David ; Committee members: Dias, Brian; Gourley, Shannon; Faundez, Victor; Holmes, Philip.
Keywords: Galanin; Withdrawal; Locus coeruleus; Ventral tegmental area; Opioid

Local Note:

ProQuest digital dissertation copies of Emory dissertations may be downloaded free of charge by Emory faculty, students, and staff unless the author has chosen to embargo the work.

Additional Identifiers

Catalog ID (MMSID):

9937407786202486

ISBN:

9798534696240