Activation of Basolateral Amygdala to Nucleus Accumbens Projection Neurons Attenuates Chronic Corticosterone-Induced Behavioral Deficits in Male Mice.

Andrew Dieterich,Benjamin A Samuels,Joseph Floeder,David J Barker,Prachi Srivastava,Jay Lee,Karina Stech

doi:10.3389/fnbeh.2021.643272

Andrew Dieterich, Benjamin A Samuels + Show 5 more

Open Access

https://doi.org/10.3389/fnbeh.2021.643272

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Abstract

The basolateral amygdala (BLA) is critical for reward behaviors via a projection to the nucleus accumbens (NAc). Specifically, BLA-NAc projections are involved in reinforcement learning, reward-seeking, sustained instrumental responding, and risk behaviors. However, it remains unclear whether chronic stress interacts with BLA-NAc projection neurons to result in maladaptive behaviors. Here we take a chemogenetic, projection-specific approach to clarify how NAc-projecting BLA neurons affect avoidance, reward, and feeding behaviors in male mice. Then, we examine whether chemogenetic activation of NAc-projecting BLA neurons attenuates the maladaptive effects of chronic corticosterone (CORT) administration on these behaviors. CORT mimics the behavioral and neural effects of chronic stress exposure. We found a nuanced role of BLA-NAc neurons in mediating reward behaviors. Surprisingly, activation of BLA-NAc projections rescues CORT-induced deficits in the novelty suppressed feeding, a behavior typically associated with avoidance. Activation of BLA-NAc neurons also increases instrumental reward-seeking without affecting free-feeding in chronic CORT mice. Taken together, these data suggest that NAc-projecting BLA neurons are involved in chronic CORT-induced maladaptive reward and motivation behaviors.

Highlights

Millions of people suffer at least one episode of major depressive disorder (MDD) in their lifetime (Hasin et al, 2005)
Eight-week-old C57BL/6J male mice were infused with Cre-dependent GqDREADD, Gi-designer receptors exclusively activated by designer drugs (DREADDs), or mCherry viruses in basolateral amygdala (BLA) and retrograde Cre virus in nucleus accumbens (NAc) (Figures 1A,B; Supplementary Figure 4) and starting 4 weeks later were trained and tested in a progressive ratio (PROG), sucrose preference (SPT), OFT, and novelty suppressed feeding (NSF) (Figure 1A)
We found that activation of NAc-projecting BLA neurons, which we hypothesized would affect motivation and reward behaviors, reversed the maladaptive chronic CORT-induced increase in NSF latency to eat

Summary

Introduction

Millions of people suffer at least one episode of major depressive disorder (MDD) in their lifetime (Hasin et al, 2005). Reward learning and responsiveness to social or monetary rewards are decreased in patients diagnosed with depression (Pizzagalli et al, 2008; Pechtel et al, 2013; Vrieze et al, 2013). This maladaptive reward processing may be due to reduced activation of important brain areas such as the nucleus accumbens (NAc) in depressed patients (Pizzagalli et al, 2009; Dillon et al, 2014). The changes in neural circuitry mediating stress effects on maladaptive reward and anhedonia are not fully understood (Russo and Nestler, 2013). A better understanding of this neural circuitry will help elucidate effective treatment strategies that provide targeted therapies to diagnosed patients (Cuthbert and Insel, 2013)

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