12 research outputs found
Prolonged Depression-Like Behavior Caused by Immune Challenge: Influence of Mouse Strain and Social Environment
Immune challenge by bacterial lipopolysaccharide (LPS) causes short-term
behavioral changes indicative of depression. The present study sought to explore
whether LPS is able to induce long-term changes in depression-related behavior
and whether such an effect depends on mouse strain and social context. LPS (0.83
mg/kg) or vehicle was administered intraperitoneally to female CD1 and C57BL/6
mice that were housed singly or in groups of 4. Depression-like behavior was
assessed with the forced swim test (FST) 1 and 28 days post-treatment.
Group-housed CD1 mice exhibited depression-like behavior 1 day post-LPS, an
effect that leveled off during the subsequent 28 days, while the behavior of
singly housed CD1 mice was little affected. In contrast, singly housed C57BL/6
mice responded to LPS with an increase in depression-like behavior that was
maintained for 4 weeks post-treatment and confirmed by the sucrose preference
test. Group-housed C57BL/6 mice likewise displayed an increased depression-like
behavior 4 weeks post-treatment. The behavioral changes induced by LPS in
C57BL/6 mice were associated with a particularly pronounced rise of
interleukin-6 in blood plasma within 1 day post-treatment and with changes in
the dynamics of the corticosterone response to the FST. The current data
demonstrate that immune challenge with LPS is able to induce prolonged
depression-like behavior, an effect that depends on genetic background (strain).
The discovery of an experimental model of long-term depression-like behavior
after acute immune challenge is of relevance to the analysis of the epigenetic
and pathophysiologic mechanisms of immune system-related affective
disorders
Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging
Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse
Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats
RATIONALE: Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. METHODS: Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. RESULTS: PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. CONCLUSIONS: PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD