Trends in Psychiatry and Psychotherapy
https://trends.org.br/article/doi/10.1590/2237-6089-2015-0017
Trends in Psychiatry and Psychotherapy
Original Article

Ethanol during adolescence decreased the BDNF levels in the hippocampus in adult male Wistar rats, but did not alter aggressive and anxiety-like behaviors

O etanol durante a adolescência reduziu os níveis de BDNF no hipocampo de ratos Wistar machos adultos, mas não alterou os comportamentos agressivos e a ansiedade

Letícia Scheidt; Gabriel Rodrigo Fries; Laura Stertz; João Carlos Centurion Cabral; Flávio Kapczinski; Rosa Maria Martins de Almeida

http://dx.doi.org/10.1590/2237-6089-2015-0017 Trends Psychiatry Psychother, vol.37, n3, p.143-151, 2015
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Abstract

Objective:To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers.Methods:Groups of male Wistar rats (mean weight 81.4 g, n = 36) were housed in groups of four until postnatal day (PND) 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16), 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12), or water (n = 12) every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test) and anxiety-like behaviors (elevated plus maze) during adulthood.Results:Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex.Conclusions:Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.

Keywords

Adolescence, alcohol abuse, aggression, anxiety, brain-derived neurotrophic factor

Resumo

Objetivo: Investigar os efeitos da exposição ao etanol em ratos adolescentes durante a idade adulta sobre os comportamentos agressivos e semelhantes à ansiedade, bem como sobre as medidas de níveis de marcadores inflamatórios.Métodos:Os grupos de ratos Wistar machos (peso médio de 81,4 g; n = 36) foram alojados em grupos de quatro até o dia pós-natal (DPN) 60. Entre os DPNs 30 e 46, os ratos receberam um dos três tratamentos: 3 g/kg de etanol (15% w/v, oralmente, n = 16), 1.5 g/kg de etanol (12,5% w/v, oralmente, n = 12), ou água (n = 12) a cada 48 horas. Os comportamentos agressivos (teste residente-intruso) e semelhantes à ansiedade (labirinto em cruz elevado) foram avaliados durante a idade adulta dos animais.Resultados:Os animais que receberam doses menores de álcool mostraram níveis reduzidos de fator neurotrófico derivado do cérebro (BDNF) no hipocampo quando comparados ao grupo controle. Nenhuma diferença significativa foi verificada no córtex pré-frontal.Conclusões:A exposição intermitente ao álcool durante a adolescência é associada com menores níveis de BDNF no hipocampo, provavelmente divido a administração episódica de álcool, mas o uso não alterou o nível de agressão contra o macho intruso ou os comportamentos semelhantes à ansiedade durante a fase adulta.

Palavras-chave

Adolescência, abuso de álcool, agressão, ansiedade, fator neurotrófico derivado do cérebro

References

Dahl RE. Adolescent brain development: a period of vulnerabilities and opportunities. Keynote address. Ann N Y Acad Sci. 2004;1021:1-22.

Crews F, He J, Hodge C. Adolescent cortical development: a critical period of vulnerability for addiction. Pharmacol Biochem Behav. 2007;86:189-99.

Spear LP. Adolescent brain development and animal models. Ann N Y Acad Sci. 2004;1021:23-6.

Crews FT, Mdzinarishvili A, Kim D, He J, Nixon K. Neurogenesis in adolescent brain is potently inhibited by ethanol. Neuroscience. 2006;137:437-45.

Spear LP, Varlinskaya EI. Adolescence. Recent developments in alcoholism.Volume 17. 2005:143-59.

Crews FT, Nixon K. Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol. 2009;44:115-27.

Brown SA, Tapert SF. Adolescence and the trajectory of alcohol use: basic to clinical studies. Ann N Y Acad Sci. 2004;1021:234-44.

You Z, Luo C, Zhang W, Chen Y, He J, Zhao Q. Pro- and anti-inflammatory cytokines expression in rat's brain and spleen exposed to chronic mild stress: involvement in depression. Behav Brain Res. 2011;225:135-41.

Rettori V, Fernandez-Solari J, Prestifilippo JP, Mohn C, De Laurentiis A, Bornstein SR. Endocannabinoids in TNF-alpha and ethanol actions. Neuroimmunomodulation. 2007;14:188-92.

Moore KW, O'Garra A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10. Annu Rev Immunol. 1993;11:165-90.

Vitkovic L, Konsman JP, Bockaert J, Dantzer R, Homburger V, Jacque C. Cytokine signals propagate through the brain. Mol Psychiatry. 2000;5:604-15.

Collins MA, Neafsey EJ. Neuroinflammatory pathways in binge alcohol-induced neuronal degeneration: oxidative stress cascade involving aquaporin, brain edema, and phospholipase A2 activation. Neurotox Res. 2012;21:70-8.

Maggs JL, Schulenberg JE. Initiation and course of alcohol consumption among adolescents and young adults. Recent developments in alcoholism.Volume 17. 2005:29-47.

Perry CL, Williams CL, Komro KA, Veblen-Mortenson S, Forster JL, Bernstein-Lachter R. Project Northland high school interventions: community action to reduce adolescent alcohol use. Health Educ Behav. 2000;27:29-49.

Pascual M, Blanco AM, Cauli O, Miñarro J, Guerri C. Intermittent ethanol exposure induces inflammatory brain damage and causes long-term behavioural alterations in adolescent rats. Eur J Neurosci. 2007;25:541-50.

Cruz AP, Frei F, Graeff FG. Ethopharmacological analysis of rat behavior on the elevated plus-maze. Pharmacol Biochem Behav. 1994;49:171-6.

Johnston AL, File SE. Sex differences in animal tests of anxiety. Physiol Behav. 1991;49:245-50.

Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2:322-8.

Toledo-Rodriguez M, Sandi C. Stress during adolescence increases novelty seeking and risk-taking behavior in male and female rats. Front Behav Neurosci. 2011;5:17.

Robert G, Drapier D, Bentué-Ferrer D, Renault A, Reymann JM. Acute and chronic anxiogenic-like response to fluoxetine in rats in the elevated plus-maze: modulation by stressful handling. Behav Brain Res. 2011;220:344-8.

Miczek KA. A new test for aggression in rats without aversive stimulation: Differential effects of d-amphetamine and cocaine. Psychopharmacology (Berl). 1979;60:253-9.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.

de Almeida RM, Benini Q, Betat JS, Hipólide DC, Miczek KA, Svensson AI. Heightened aggression after chronic flunitrazepam in male rats: potential links to cortical and caudate-putamen-binding sites. Psychopharmacology (Berl). 2008;197:309-18.

Spanagel R, Noori HR, Heilig M. Stress and alcohol interactions: animal studies and clinical significance. Trends Neurosci. 2014;37:219-27.

Walker BM, Ehlers CL. Age-related differences in the blood alcohol levels of Wistar rats. Pharmacol Biochem Behav. 2009;91:560-5.

Casey BJ, Jones RM. Neurobiology of the adolescent brain and behavior: implications for substance use disorders. J Am Acad Child Adolesc Psychiatry. 2010;49:1189-201.

McBride WJ, Bell RL, Rodd ZA, Strother WN, Murphy JM. Adolescent alcohol drinking and its long-range consequences. Recent developments in alcoholism.Volume 17. 2005:123-42.

Kane CJ, Phelan KD, Douglas JC, Wagoner G, Johnson JW, Xu J. Effects of ethanol on immune response in the brain: region-specific changes in aged mice. J Neuroinflammation. 2013;10:66.

Jerrells TR, Weinberg J. Influence of ethanol consumption on immune competence of adult animals exposed to ethanol in utero. Alcohol Clin Exp Res. 1998;22:391-400.

Davis MI. Ethanol-BDNF interactions: still more questions than answers. Pharmacol Ther. 2008;118:36-57.

Moonat S, Starkman BG, Sakharkar A, Pandey SC. Neuroscience of alcoholism: molecular and cellular mechanisms. Cell Mol Life Sci. 2010;67:73-88.

MacLennan AJ, Leea N, Walker DW. Chronic ethanol administration decreases brain-derived neurotrophic factor gene expression in the rat hippocampus. Neurosci Lett. 1995;197:105-8.

Cook RT. Alcohol abuse, alcoholism, and damage to the immune system-a review. Alcohol Clin Exp Res. 1998;22:1927-42.

Witt ED. Research on alcohol and adolescent brain development: opportunities and future directions. Alcohol. 2010;44:119-24.

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