Exploring the effects of adolescent social isolation stress on the serotonin system and ethanol-motivated behaviors

Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Rationale Alcohol is one of the most frequently used drugs abuse and has a major impact on human health worldwide. People assigned female at birth those with adverse childhood experiences are stress-vulnerable more likely to report drinking as means “self-medication.” Prior studies in our laboratory showed that adolescent social isolation stress (SIS) increases vulnerability ethanol (EtOH) intake consumption despite negative consequences rats. Objectives Here, we explored modulation dorsal raphe nucleus (DRN)-serotonin (5-HT) system, sexually dimorphic neurotransmitter system involved stress-reward interactions, determine its contribution EtOH-motivated behaviors rats have undergone SIS. Results We employed electrophysiological functional neuroanatomy strategies show both SIS EtOH exposure induce persistent hypofunction DRN 5-HT particularly females. Chemogenetic activation neurons attenuated reward value for sucrose elevated punished responding stress-dependent manner. Conclusions Our results highlight an inverse relationship between sex- nature this relationship, connection signaling acute rewards punishment. These data support potential target treat aberrant alcohol populations.

Language: Английский

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Voluntary adolescent alcohol exposure does not increase adulthood consumption of alcohol in multiple mouse and rat models

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Adolescence is a period of increased risk taking, including alcohol and drug use. Multiple clinical studies report positive relationship between adolescent consumption developing an use disorder (AUD) in adulthood. However, few preclinical have attempted to tease apart the biological contributions exposure, independent other social, environmental, stress factors, that been conducted show mixed results. Here we several voluntary models, across four labs three institutes with two rodent species, investigate ramifications on adulthood controlled, pre-clinical environments. We consistently demonstrate lack robust increases consumption. This work highlights risks seen both human datasets murine drinking models may be due unique social environmental factors - some which humans.

Language: Английский

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Effects of early social isolation and adolescent single prolonged stress on anxiety‐like behaviors and voluntary ethanol consumption in female Long Evans rats

Alcohol Clinical and Experimental Research, Journal Year: 2024, Volume and Issue: 48(8), P. 1586 - 1599

Published: June 20, 2024

Exposure to stress during childhood and adolescence is a risk factor for alcohol use disorder (AUD) comorbid conditions, including posttraumatic (PTSD). We previously established an adolescent social isolation (SI) model that leads the emergence of wide range behavioral factors AUD, increased anxiety-like behavior, locomotor activity, ethanol consumption in male female rats. Here, we sought test hypothesis SI may increase vulnerability single prolonged (SPS), rodent PTSD.

Language: Английский

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Is the Relationship Between Adolescent Social Isolation and Anxiety‐Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats?

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Despite extensive, cross-disciplinary research revealing a relationship between early life stress (ELS) and an increased risk for neuropsychiatric disorders, the underlying processes mediating this are not fully understood. Further, majority of preclinical studies investigating have taken sex differences into consideration. A growing body work suggests that microglia, resident immune cells brain, impacted by ELS contribute to some maladaptive behavioral phenotypes in adulthood. Here, we utilized adolescent social isolation (aSI) model female rats test role microglia effects on anxiety-related behaviors. The present study sought determine whether ablation during aSI could prevent anxiety-like behaviors Long Evans rats. colony-stimulating factor 1 receptor (CSF1-r) inhibitor, PLX3397, was provided chow ablate at start period (postnatal day (P) 21-42). During period, animals performed battery assays including open field test, elevated plus maze, successive alleys test. Following completion assays, brain tissue collected confirm efficacy PLX3397 identify changes population density. Relative group-housed (GH) controls, showed locomotor activity higher closed-arm entries maze. Although effectively ablated across all animals, treatment had minimal observed aSI-associated phenotypes. Together, these data suggest required adaptations promoted aSI. Future will be needed assess

Language: Английский

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Effects of social isolation on locus coeruleus opioid receptor expression and affective behavior.

Neurobiology of Stress, Journal Year: 2025, Volume and Issue: unknown, P. 100717 - 100717

Published: March 1, 2025

Language: Английский

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Voluntary adolescent alcohol exposure does not robustly increase adulthood consumption of alcohol in multiple mouse and rat models

Addiction Neuroscience, Journal Year: 2024, Volume and Issue: 12, P. 100171 - 100171

Published: Aug. 3, 2024

Adolescence is a period of increased risk taking, including alcohol and drug use. Multiple clinical studies report positive relationship between adolescent consumption developing an use disorder (AUD) in adulthood. However, few preclinical have attempted to tease apart the biological contributions exposure, independent other social, environmental, stress factors, that been conducted show mixed results. Here we several voluntary models, across four labs three institutes with two rodent species, investigate ramifications on adulthood controlled, pre-clinical environments. We consistently demonstrate lack robust increases consumption. This work highlights risks seen both human datasets murine drinking models may be due unique social environmental factors - some which humans.

Language: Английский

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Crocin has a greater therapeutic role in the restoration of behavioral impairments caused by maternal social isolation in adolescent than in adult offspring probably through GSK-3beta downregulation

Learning and Motivation, Journal Year: 2024, Volume and Issue: 88, P. 102060 - 102060

Published: Oct. 23, 2024

Language: Английский

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Sex-specific changes in voluntary alcohol consumption and nucleus accumbens synaptic plasticity in C57BL/6J mice exposed to neonatal maternal separation

Neuropharmacology, Journal Year: 2024, Volume and Issue: 262, P. 110212 - 110212

Published: Nov. 7, 2024

The long-term influence of early-life stress on brain neurophysiology has been extensively investigated using different animal models. Among these, repeated maternal separation (RMS) in rodents is one the most commonly adopted. In this study, we elucidated long-lasting effects exposure to postnatal RMS C57BL/6J adult mice voluntary alcohol consumption and nucleus accumbens (NAc) neurophysiology. Mice were separated from their dam for 360 min daily day 2 (PND2) PND17, experiments then performed (PND60) animals. addition, as recent evidence showed that circulating estrogens may play a protective role against function, including organization activation neuronal structures, also evaluated effect single injection β-estradiol 3-benzoate (EB) at PND2, which known disrupt male sex differentiation, mice. was associated with an increased preference mice, but not female or treated EB. Patch clamp conducted NAc medium spiny neurons (MSNs) revealed excitatory inhibitory synaptic transmission plasticity glutamatergic synapses significantly impaired exposed protocol. This again prevented Our findings strengthen idea sex-dependent modifications areas involved goal-directed behavior intake.

Language: Английский

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Effects of Social Isolation on Locus Coeruleus Opioid Receptor Expression and Affective Behavior

Published: Jan. 1, 2024

Language: Английский

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Hippocampal Viral-Mediated Urokinase Plasminogen Activator (uPA) Overexpression Mitigates Stress-Induced Anxiety and Depression in Rats by Increasing Brain-Derived Neurotrophic Factor (BDNF) Levels

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1603 - 1603

Published: Dec. 15, 2024

Emerging evidence suggests the serine protease, urokinase plasminogen activator (uPA), may play an important role in modulation of mood and cognitive functions. Also, preliminary indicates that uPA modulates BDNF activity is known to be involved pathogenesis disorders. However, physiological functions specific brain regions for mediating stress-related emotional behaviors remain elucidated. Therefore, aim this study was assess ectopic expression on anxiety- depression-like following social defeat stress rats. For purpose, we inspected behavioral outcomes bilateral stereotaxic delivery uPA-overexpressing lentiviral vectors hippocampus using a series tests. Results show hippocampal gain-of-function prevented stress-elicited anxiogenic-like effects, as determined marble burying, open field, elevated plus maze tests, with no alterations spontaneous locomotor activity. overexpression resulted anti-depressant-like effects sucrose splash, tail suspension, forced swim Most importantly, increased levels, strong positive correlation found Pearson test. Moreover, same analysis revealed negative relationship between mRNA parameters behaviors. Taken together, work highlights importance considering activation provides new insights into mechanisms pathophysiology illnesses, which should help development approaches tackle depression anxiety

Language: Английский

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