URB597 ameliorates the deleterious effects induced by binge alcohol consumption in adolescent rats

Paula M.Q. Bellozi, R. Pelição, Matheus C. Santos, Isabel V.A. Lima, Soraya W. Saliba, Érica L.M. Vieira, Alline C. Campos, Antônio L. Teixeira, Antônio C.P. de Oliveira, Ester M. Nakamura-Palacios, Lívia C.M. Rodrigues

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Heavy episodic drinking or binge drinking during adolescence may elicit serious neurotoxic consequences in cerebral areas (e.g., the prefrontal cortex, i.e., PFC) and the hippocampus, delay the maturation of the brain and increase the probability of drug abuse and dependence. The endocannabinoid system plays an important role in neuroprotection by reducing oxidative stress and neuroinflammation. In the present study, we aimed to investigate whether URB597, an inhibitor of the metabolic enzyme of the endocannabinoid anandamide (AEA), altered the effects of acute and chronic alcohol administration beginning during rat adolescence on recognition memory, neuroinflammation and brain-derived neurotrophic factor (BDNF) levels. The animals received intraperitoneal injections of URB597 (0.3 mg/Kg) or vehicle followed by the oral administration of ethanol (3 or 6 g/Kg) or distilled water for 3 consecutive days in one week (acute binging) or over 4 weeks (chronic binging). The groups were submitted to the novel object recognition task, and their PFCs and hippocampi were removed for analyses of the cytokine and BDNF levels. URB597 potentiated long-term memory after the 3 mg/Kg acute alcohol administration. The chronic binge alcohol administration increased the interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels in the PFC and hippocampus and the interleukin (IL)-10 and BDNF levels in the PFC, and these effects were prevented by URB597. Our results indicate that the neuromodulation facilitated by AEA can reduce the neuroimmune response induced by the chronic administration of alcohol beginning in adolescence in rats.

Original languageEnglish (US)
Article number134408
JournalNeuroscience Letters
Volume711
DOIs
StatePublished - Oct 15 2019
Externally publishedYes

Keywords

  • Adolescence
  • Alcohol binging
  • Endocannabinoid system
  • Neuroinflammation
  • URB597

ASJC Scopus subject areas

  • General Neuroscience

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