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EXAMINING THE ROLE OF BASOLATERAL AMYGDALA CIRCUITRY IN ALCOHOL DRINKING BEHAVIORS AND A MODEL OF ADDICTION VULNERABILITY

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abstract
Alcohol use disorder (AUD) represents a major health and economic problem world-wide. It is a chronic, relapsing disease characterized by a transition from drinking for the pleasurable effects of alcohol into a loss of control over alcohol drinking driven, in part, by the emergence of negative emotional states in withdrawal and abstinence. As such, AUD is highly comorbid with anxiety/stressor-related disorders and this comorbidity is associated with greater symptom severity and a poorer prognosis in recovery. The co-occurrence of these disorders is associated with common maladaptive neurobiological alterations. One brain region known to play a role in the etiology of AUD and anxiety/stressor-related disorders is the basolateral amygdala (BLA). Despite many studies implicating BLA hyperexcitability in AUD and anxiety/stressor-related disorders, little is known about the specific efferent projections from the BLA that contribute to these disorders. Recent optogenetic studies have shown that the BLA sends monosynaptic glutamatergic projections to both the ventral hippocampus (vHC) and nucleus accumbens (NAc). The BLA-vHC circuit has been shown to modulate both fear- and anxiety-related behaviors, while the BLA-NAc core circuit has been shown to modulate motivation for drug taking and seeking. In chapters 2 and 3, we sought to examine the role of a BLA-vHC and a BLA-NAc core circuit in ethanol drinking- related behaviors using a limited-access operant ethanol self-administration procedure that procedurally separates appetitive (i.e. seeking) and consummatory (i.e. intake) drinking related behaviors. In chapter 2, we build upon previous findings, showing that chemogenetically silencing a BLA-vHC circuit reduces anxiety-like behaviors on the elevated plus-maze. Moreover, we report, for the first time, that chemogenetically silencing this circuit reduces appetitive and consummatory ethanol drinking-related behaviors. Silencing this circuit also reduced drinking measures in rats trained to self-administer a sucrose solution, however most of these effects were more modest than those observed in ethanol drinking subjects. In chapter 3, we found that chemogenetically silencing a BLA-NAc core circuit had no effects on consummatory behaviors for either ethanol or sucrose but produced dissociable effects on ethanol and sucrose appetitive measures. Upon intra-NAc core CNO infusion in animals expressing Gi-DREADD we found that lever pressing for ethanol was reduced while this measure was actually increase in sucrose drinking subjects. Notably, these divergent effects on appetitive behaviors were observed in the absence of any changes in anxiety- or depressive-like behaviors. In the discussion of this chapter, we propose a hypothesis that may reconcile these surprising findings, based on emerging evidence of the complexity of the BLA efferent circuits that govern positive and negative valence.
subject
contributor
Ewin, Sarah (author)
Weiner, Jeffrey L (committee chair)
Ma, Tao (committee member)
McCool, Brian A (committee member)
Chen, Rong (committee member)
Jones, Sara R (committee member)
date
2019-05-24T08:35:42Z (accessioned)
2019-05-24T08:35:42Z (available)
2019 (issued)
degree
Physiology and Pharmacology (discipline)
identifier
http://hdl.handle.net/10339/93942 (uri)
language
en (iso)
publisher
Wake Forest University
title
EXAMINING THE ROLE OF BASOLATERAL AMYGDALA CIRCUITRY IN ALCOHOL DRINKING BEHAVIORS AND A MODEL OF ADDICTION VULNERABILITY
type
Dissertation

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