Effects of Adverse Maternal Care on Development of the Prefrontal Cortex, Amygdala, Hippocampus and Nucleus Accumbens in Rhesus Monkeys: Relations with Cocaine Self-Administration Open Access

Kochoian, Brik (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/sn009z60w?locale=en


Childhood is a critical period for neurodevelopment, which can be strongly influenced by social, sensory and stressful experiences. The goal of this study was to examine the impact of early life stress (ELS) on brain structural development by focusing on the development of the amygdala and hippocampus (due to their critical role in stress and emotional regulation and their connections with reward regions), the prefrontal cortex (PFC) (due to its critical role in cognitive control of behavior, goal-directed behaviors, impulse/perseverative control, reward associations, emotional regulation, response inhibition, and top-down control of reward centers), and the nucleus accumbens (NAcc) due to its role in reward processes and reinforcing effects of psychostimulants such as cocaine (COC). The main goal was to identify neurodevelopmental underpinnings linking ELS and psychostimulant escalation using a non-human primate (NHP) of infant maltreatment and a COC self-administration (SA) paradigm during adolescence. We examined the impact of ELS, defined by a naturalistic infant maltreatment model, on longitudinal structural development of those brain regions using structural MRI scans acquired at 3, 6, and 12 months of age. Confounding effects of heritability were controlled for by using a unique cross-fostering paradigm, in which all subjects were randomly assigned to either a maltreating or control mother at birth. Furthermore, we also examined whether subjects who had been maltreated during infancy were more vulnerable than controls on a COC SA escalation paradigm during adolescence. This study found region-specific impacts of ELS on brain development in the amygdala and NAcc, but not the PFC or hippocampus. Furthermore, we did not observe ELS-related differences on COC SA escalation measures, either. These findings suggest that ELS has a negative impact on neurodevelopment, with region-specific effects on amygdala and NAcc development, but not the PFC or hippocampus. Furthermore, our findings also suggest that all subjects, regardless of rearing, self-administer COC at comparable levels during the phases of the COC SA paradigm analyzed in this study.

Table of Contents

Table of Contents

Abstract 4



ELS as a Risk for Developmental Psychopathology, Including Substance Use Disorders (SUDs): Impact on Prefrontal-Limbic Regions that Regulate Emotional/Stress Responses & Reward Processes. 10

Macaque Model of ELS—Induced Risk for Adolescence Drug Addiction. 16

Adolescence Brain Remodeling & Risk for Psychostimulant Drug Initiation and Addiction: 18



Subjects and Housing. 24

Cross-fostering Design & Naturalistic Maltreatment Model 26

Structural MRI Image Acquisition. 27

MRI Data Processing, Analysis and Region of Interest (ROI) Volume Computation. 28

Neuroanatomical Definitions of Regions of Interest (ROI) in the Atlas. 30

Cocaine self-administration (COC SA) 31

Drugs. 31

COC SA procedures. 31

Training. 31

Limited Access (LA) 32

Extended Access (EA) 32

Data Analyses. 33

Structural MRI data. 33

Cocaine Self-Administration (COC SA) 34


Ø     Structural MRI Measures. 35

Intracranial Volume (ICV) 35

Total WM, GM, and CSF Volumes. 35

Hippocampal Volume. 35

Amygdala Volume. 36

PFC Volume. 38

Total PFC Volume (GM+WM) 38

Total PFC GM... 38

Total PFC WM... 39

OFC Volume. 40

v    OFC Brodmann Area 11 Volume. 40

v    OFC Brodmann Area 13 Volume. 40

ACC Brodmann Area 24 Volume. 40

mPFC Volume. 40

v    mPFC Brodmann Area 25. 40

v    mPFC Brodmann Area 32. 41

DLPFC Brodmann Area 46 Volume. 41

NAcc Volume. 41

Ø     Cocaine Self-Administration. 42

Average Response Rate. 42

Average Time to Obtain 20 Reinforcers. 42




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