Neurodevelopmental origins of substance use disorders: Evidence from animal models of early‐life adversity and addiction

European Journal of Neuroscience, Год журнала: 2021, Номер 55(9-10), С. 2170 - 2195

Опубликована: Апрель 7, 2021

Addiction is a chronic relapsing disorder with devastating personal, societal, and economic consequences. In humans, early-life adversity (ELA) such as trauma, neglect, resource scarcity are linked increased risk of later-life addiction, but the brain mechanisms underlying this link still poorly understood. Here, we focus on data from rodent models ELA in which causal effects responses to drugs neurodevelopmental by increases vulnerability addiction can be determined. We first summarize evidence for between then describe how commonly modeled rodents. Since heterogeneous disease many individually varying behavioral aspects that may impacted ELA, next discuss common assays addiction-like behaviors. specific addiction-relevant phenotypes caused male female rodents some changes reward stress circuits likely responsible. By better understanding neural promotes vulnerability, hope facilitate development new approaches preventing or treating those history ELA.

Язык: Английский

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Enduring disruption of reward and stress circuit activities by early-life adversity in male rats

Translational Psychiatry, Год журнала: 2022, Номер 12(1)

Опубликована: Июнь 16, 2022

Abstract In humans, early-life adversity (ELA) such as trauma, poverty, and chaotic environment is linked to increased risk of later-life emotional disorders including depression substance abuse. These involve underlying disruption reward circuits likely vary by sex. Accordingly, we previously found that ELA leads anhedonia for natural rewards cocaine in male rodents, whereas females instead increases vulnerability addiction-like use opioid drugs palatable food. While these findings suggest ELA-induced circuitry may differ between the sexes, specific circuit nodes are influenced either sex remain poorly understood. Here, adult Sprague-Dawley rats, ask how impacts addiction-relevant behaviors tested after females. We probe potential mechanisms males assessing opioid-associated neuronal activation stress nucleus accumbens (NAc), amygdala, medial prefrontal cortex (mPFC), paraventricular thalamus. find diminishes opioid-seeking males, alters heroin-induced NAc, PFC, suggesting a circuit-based mechanism. studies demonstrate behavioral neurobiological disruptions consistent with unlike seeking saw Our findings, taken together our prior work, men women could face qualitatively different mental health consequences ELA, which be essential individually tailoring future intervention strategies.

Язык: Английский

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Early Life Adversity and Neuropsychiatric Disease: Differential Outcomes and Translational Relevance of Rodent Models

Frontiers in Systems Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Июнь 23, 2022

It is now well-established that early life adversity (ELA) predisposes individuals to develop several neuropsychiatric conditions, including anxiety disorders, and major depressive disorder. However, ELA a very broad term, encompassing multiple types of negative childhood experiences, physical, sexual emotional abuse, physical neglect, as well trauma associated with chronic illness, family separation, natural disasters, accidents, witnessing violent crime. Emerging literature suggests in humans, different adverse experiences are more or less likely produce susceptibilities certain conditions involve affective dysfunction. To investigate the driving mechanisms underlying connection between experience subsequent disease, neuroscientists have developed rodent models ELA, pain exposure, maternal deprivation, limited resources. These studies also shown paradigms but somewhat overlapping behavioral phenotypes. In this review, we first may be outcomes brain changes humans. We next evaluate whether can provide translationally relevant information regarding links specific neural circuits

Язык: Английский

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Practical solutions for including sex as a biological variable (SABV) in preclinical neuropsychopharmacological research

Journal of Neuroscience Methods, Год журнала: 2023, Номер 401, С. 110003 - 110003

Опубликована: Ноя. 1, 2023

Язык: Английский

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Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions

Frontiers in Behavioral Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Май 27, 2020

Forced abstinence (FA) from alcohol has been shown to produce a variety of anxiety- and depression-like symptoms in animal models. Somatostatin (SST) neurons, subtype GABAergic neurons found throughout the brain, are novel neural target with potential treatment implications affective disorders, yet their role use disorders (AUD) remains be explored. Here, we examined neuroadaptations SST during forced voluntary consumption. Following 6 weeks two-bottle choice consumption protracted abstinence, male female C57BL/6J mice exhibited heightened, but sex-specific, depressive-like behavioral profile sucrose preference test (SPT) swim (FST), without changes anxiety-like behaviors elevated plus maze (EPM) open field (OFT). FST-induced cFos expressions prefrontal cortex (PFC) ventral bed nucleus stria terminalis (vBNST) were altered FA-exposed only, suggesting sex-specific effect on response acute stress. immunoreactivity these regions was unaffected by while differences seen SST/cFos co-expression vBNST. No or lateral central amygdala (CEA) basolateral (BLA). Additionally, displayed opposing alterations PFC vBNST, heightened intrinsic excitability diminished These findings provide an overall framework abstinence-induced key brain involved emotional regulation processing.

Язык: Английский

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An Adolescent Sensitive Period for Threat Responding: Impacts of Stress and Sex

Biological Psychiatry, Год журнала: 2020, Номер 89(7), С. 651 - 658

Опубликована: Окт. 10, 2020

Язык: Английский

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Early life adversity predicts brain-gut alterations associated with increased stress and mood

Neurobiology of Stress, Год журнала: 2021, Номер 15, С. 100348 - 100348

Опубликована: Май 25, 2021

Alterations in the brain-gut system have been implicated various disease states, but little is known about how early-life adversity (ELA) impacts development and adult health as mediated by interactions. We hypothesize that ELA disrupts components of system, thereby increasing susceptibility to disordered mood. In a sample 128 healthy participants, history current stress, depression, anxiety were assessed using validated questionnaires. Fecal metabolites measured liquid chromatography tandem mass spectrometry-based untargeted metabolomic profiling. Functional brain connectivity was evaluated magnetic resonance imaging. Sparse partial least squares-discriminant analysis, controlling for sex, body index, age, diet used predict alterations function ELA. correlated with four gut-regulated within glutamate pathway (5-oxoproline, malate, urate, gamma methyl ester) functional primarily sensorimotor, salience, central executive networks. Integrated analyses revealed significant associations between these metabolites, connectivity, scores perceived anxiety, depression. This study reveals novel association ELA, axis, increased vulnerability negative mood stress. Results from raise hypothesis select may contribute adverse effects critical period stress on neural via pathways related glutamatergic excitotoxicity oxidative

Язык: Английский

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A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Developmental Cognitive Neuroscience, Год журнала: 2021, Номер 48, С. 100924 - 100924

Опубликована: Янв. 27, 2021

Adversity early in life substantially impacts prefrontal cortex (PFC) development and vulnerability to later-life psychopathology. Importantly, repeated adverse experiences throughout childhood increase the risk for PFC-mediated behavioral deficits more commonly women. Evidence from animal models points effects of adversity on neural dysfunction; however, few studies have investigated neurobiological underpinnings sex-specific, long-term consequences multiple developmental stressors. We modeled rats via maternal separation (postnatal day (P)2-20) juvenile social isolation (P21-35). In adulthood, anxiety-like behavior was assessed elevated zero maze presence structural integrity PFC perineuronal nets (PNNs) enwrapping parvalbumin (PV)-expressing interneurons quantified. PNNs are extracellular matrix structures formed during critical periods postnatal that play a key role plasticity PV cells. observed female-specific effect hyperactivity risk-assessment behavior. Moreover, females - but not males exposed hits demonstrated reduction cells adulthood. also potentiated + PNN integrity. These findings suggest sex-specific impact neurostructural implicate as contributor associated dysfunction.

Язык: Английский

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Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance

Frontiers in Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Янв. 4, 2022

Early life stress is thought to be a risk factor for emotional disorders, particularly depression and anxiety. Although the excitation/inhibition (E/I) imbalance has been implicated in neuropsychiatric whether early affects E/I balance medial prefrontal cortex at various developmental stages unclear. In this study, rats exposed maternal separation (MS) that exhibited well-established paradigm were used evaluate adolescence (postnatal day P43-60) adulthood (P82-100) by behavior tests, whole-cell recordings, microdialysis coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. First, behavioral tests revealed MS induced both anxiety- depressive-like behaviors adolescent but only adult rats. Second, increased action potential frequency of synaptic transmission onto L5 pyramidal neurons prelimbic (PrL) brain region while decreasing Finally, increases extracellular glutamate levels decreased paired-pulse ratio evoked excitatory postsynaptic currents (EPSCs) PrL contrast, EPSCs The present results reveal key role different MS-induced disorders may related altered probability presynaptic release stages.

Язык: Английский

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Sex differences in addiction-relevant behavioral outcomes in rodents following early life stress

Addiction Neuroscience, Год журнала: 2023, Номер 6, С. 100067 - 100067

Опубликована: Янв. 26, 2023

In humans, exposure to early life stress (ELS) is an established risk factor for the development of substance use disorders (SUDs) during later life. Similarly, rodents exposed ELS involving disrupted mother-infant interactions, such as maternal separation (MS) or adverse caregiving due scarcity-adversity induced by limited bedding and nesting (LBN) conditions, also exhibit long-term alterations in alcohol drug consumption. both humans rodents, there a range addiction-related behaviors that are associated with even predictive subsequent SUDs. these include increased anxiety-like behavior, impulsivity, novelty-seeking, altered intake patterns, well reward-related processes consummatory social behaviors. Importantly, expression often varies throughout lifespan. Moreover, preclinical studies suggest sex differences play role how impacts reward phenotypes underlying brain circuitry. Here, addiction-relevant behavioral outcomes mesolimbic dopamine (DA) dysfunction resulting from form MS LBN discussed focus on age- sex-dependent effects. Overall, findings may increase susceptibility SUDs interfering normal maturation function.

Язык: Английский

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