Regional Specificity Of Ethanol and NMDA Action in Brain Revealed With FOS-Like Immunohistochemistry and Differential Routes of Drug Administration

Knapp, Darin J.; Braun, Christopher J.; Duncan, Gary E.; Qian, Ying; Fernandes, Alda; Crews, Fulton T.; Breese, George R.

doi:10.1097/00000374-200111000-00014

Cited by 16 publications

(20 citation statements)

References 55 publications

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“…Our findings in ethanol-naïve adult Wistar rats are largely consistent with previous studies using various ethanol challenges of rats and mice (Ryabinin et al, 1999; Horn et al, 2008; May et al, 2008; Vilpoux et al, 2009) including ethanol dose-response curves as reported here (Ryabinin et al, 1997; Knapp et al, 2001). We report here that AIE results in a marked loss of the adult frontal cortical neuronal responses to ethanol challenge, a modest right shift in CeA and BLA dose responses and a significant increase in nucleus accumbens maximal responses at high ethanol doses.…”

Section: Discussionsupporting

confidence: 92%

“…Many studies have investigated ethanol induction of neuronal c-Fos and EGR1 and found that numerous and similar brain regions are activated by systemic ethanol exposure of rats and mice (Ryabinin et al, 1997, 1999; Knapp et al, 2001; Vilpoux et al, 2009). Ethanol activation of brain neurons likely occur through multiple mechanisms including directional pharmacological effects on neurons as well as through alterations in excitability through altered neuronal networks.…”

Section: Introductionmentioning

confidence: 99%

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Adolescent Intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat

Liu

Crews

2015

Neuroscience

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The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on–2 days off; P25–P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Adolescent Intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat

Liu

Crews

2015

Neuroscience

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“…An intoxicating dose of alcohol administered ip or ig modulates Fos expression in the prefrontal cortex, bed nucleus of the stria terminalis, central nucleus of the amygdala, and locus coeruleus (Chang et al, 1995; Knapp et al, 2001). These targeted regions could regulate HPA reactivity through direct or indirect pathways and provide another layer of regulation in response to alcohol stimulation (Ulrich-Lai and Herman, 2009; Herman, 2012).…”

Section: Alcohol Stimulates the Release Of Stress Hormonesmentioning

confidence: 99%

Alcohol, stress hormones, and the prefrontal cortex: A proposed pathway to the dark side of addiction

Richardson

2014

Neuroscience

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Chronic exposure to alcohol produces changes in the prefrontal cortex that are thought to contribute to the development and maintenance of alcoholism. A large body of literature suggests that stress hormones play a critical role in this process. Here we review the bi-directional relationship between alcohol and stress hormones, and discuss how alcohol acutely stimulates the release of glucocorticoids and induces enduring modifications to neuroendocrine stress circuits during the transition from non-dependent drinking to alcohol dependence. We propose a pathway by which alcohol and stress hormones elicit neuroadaptive changes in prefrontal circuitry that could contribute functionally to a dampened neuroendocrine state and the increased propensity to relapse—a spiraling trajectory that could eventually lead to dependence.

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“…1A) (33–35). Rats in the control group received either saline or an isocaloric glucose solution as indicated and were pair-fed to match caloric intake between groups.…”

Section: Resultsmentioning

confidence: 99%

“…1B, where the control group was injected with saline. Intraperitoneal injections are widely used in rodent models, and many studies have shown that oral and intraperitoneal administration yield similar results for several biological readouts (34, 35, 56, 57). Intraperitoneal administration also avoids the first-pass gastric metabolism of ethanol, which can vary depending on the nutritional state of the animal and adds an additional variable.…”

Section: Methodsmentioning

confidence: 99%

Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action

et al. 2013

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Individuals with a history of binge drinking have an increased risk of developing the metabolic syndrome and type 2 diabetes. Whether binge drinking impairs glucose homeostasis and insulin action is unknown. To test this, we treated Sprague-Dawley rats daily with alcohol (3 g/kg) for three consecutive days to simulate human binge drinking and found that these rats developed and exhibited insulin resistance even after blood alcohol concentrations had become undetectable. The animals were resistant to insulin for up to 54 hours after the last dose of ethanol, chiefly a result of impaired hepatic and adipose tissue insulin action. Because insulin regulates hepatic glucose production and white adipose tissue lipolysis, in part through signaling in the central nervous system, we tested whether binge drinking impaired brain control of nutrient partitioning. Rats that had consumed alcohol exhibited impaired hypothalamic insulin action, defined as the ability of insulin infused into the mediobasal hypothalamus to suppress hepatic glucose production and white adipose tissue lipolysis. Insulin signaling in the hypothalamus, as assessed by insulin receptor and AKT phosphorylation, decreased after binge drinking. Quantitative polymerase chain reaction showed increased hypothalamic inflammation and expression of protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling. Intracerebroventricular infusion of CPT-157633, a small-molecule inhibitor of PTP1B, prevented binge drinking–induced glucose intolerance. These results show that, in rats, binge drinking induces systemic insulin resistance by impairing hypothalamic insulin action and that this effect can be prevented by inhibition of brain PTP1B.

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Regional Specificity Of Ethanol and NMDA Action in Brain Revealed With FOS-Like Immunohistochemistry and Differential Routes of Drug Administration

Abstract: These results provide new evidence for the regionally specific functional interactions of EtOH on NMDA receptors in vivo. Moreover, these results support efforts to identify brain region-specific targets for EtOH and EtOH-induced changes in gene expression.

Cited by 16 publications

References 55 publications

Adolescent Intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat

Adolescent Intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat

Alcohol, stress hormones, and the prefrontal cortex: A proposed pathway to the dark side of addiction

Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action

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