Adolescent Ethanol Exposure Leads to Stimulus-Specific Changes in Cytokine Reactivity and Hypothalamic-Pituitary-Adrenal Axis Sensitivity in Adulthood
Autor: | Tamara L. Doremus-Fitzwater, Anny Gano, Andrew S. Vore, Terrence Deak |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
sex differences medicine.medical_specialty Lipopolysaccharide Cognitive Neuroscience medicine.medical_treatment lcsh:RC321-571 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Corticosterone Internal medicine Gene expression medicine cytokine rat lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Ethanol business.industry HPA axis Interleukin 3. Good health adolescent intermittent ethanol 030104 developmental biology Neuropsychology and Physiological Psychology medicine.anatomical_structure Cytokine Endocrinology chemistry 13. Climate action Tumor necrosis factor alpha business 030217 neurology & neurosurgery Hypothalamic–pituitary–adrenal axis Neuroscience |
Zdroj: | Frontiers in Behavioral Neuroscience Frontiers in Behavioral Neuroscience, Vol 11 (2017) |
ISSN: | 1662-5153 |
Popis: | Adolescent alcohol use comprises a significant public health concern and is often characterized by binge-like consumption patterns. While ethanol exposure in adulthood has been shown to alter the stress response, including the Hypothalamic–Pituitary–Adrenal (HPA) axis, few studies have examined whether binge-like ethanol exposure during adolescence results in enduring changes in HPA axis sensitivity in adulthood. In the present studies, adolescent Sprague-Dawley rats were given intragastric (i.g.) intubations of ethanol (4 g/kg) or vehicle once per day for three consecutive days, beginning on postnatal day (P) 30 (±1). This exposure was followed by a 2-day period of rest/withdrawal. Rats received a total of either two (Experiments 1, 2 and 3) or four (Experiment 4) cycles of ethanol exposure and were subsequently allowed to age normally until adulthood. In Experiment 1, adult, (P71–75), ethanol- or vehicle-exposed rats received a 60 min restraint stress challenge. In Experiment 2, rats received a 50 μg/kg injection of lipopolysaccharide (LPS). In Experiment 3, rats received a challenge of 2.5 g/kg ethanol (intraperitoneally; i.p.). In Experiment 4, male and female ethanol- or vehicle- exposed rats received a 50 μg/kg injection of LPS. In all experiments, blood samples were collected for later assessment of corticosterone (CORT), blood ethanol concentrations (BECs), and the cellular fraction of blood was analyzed for cytokine gene expression. As expected, all three challenges led to a time-dependent surge in CORT. Gene expression analyses of cytokines (Interleukin [IL]-6, IL-1β, and Tumor necrosis factor alpha [TNFα]) from the cellular fraction of blood revealed unique, time-dependent patterns of cytokine expression depending upon the nature of the adult challenge incurred (restraint, LPS, or EtOH). Importantly, adolescent ethanol exposure led to attenuated restraint and LPS-induced cytokine expression in males, whereas female rats displayed an absence of cytokine alterations, and a tendency toward heightened HPA axis reactivity. These findings suggest that adolescent ethanol exposure may cause lasting alterations in cytokine regulation and HPA axis sensitivity that (a) persist into adulthood; (b) may vary depending on the nature of the challenge incurred during adulthood; and that (c) are sex-specific. |
Databáze: | OpenAIRE |
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