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Behavioral and biochemical effects of ethanol withdrawal in zebrafish

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ABSTRACT Chronic alcohol use induces adaptations and toxicity that can induce symptoms of anxiety, autonomic hyperarousal, and epileptic seizures when alcohol is removed (withdrawal syndrome). Zebrafish has recently gained wide… Click to show full abstract

ABSTRACT Chronic alcohol use induces adaptations and toxicity that can induce symptoms of anxiety, autonomic hyperarousal, and epileptic seizures when alcohol is removed (withdrawal syndrome). Zebrafish has recently gained wide attention as a behavioral model to study the neurobehavioral effects of acute and chronic alcohol use, including withdrawal. The literature, however, is very contradictory on findings regarding withdrawal effects, with some studies reporting increased anxiety, while others report no effect. A meta‐analytic approach was taken to find the sources of this heterogeneity, and ethanol concentration during exposure and exposure duration were found to be the main sources of variation. A conceptual replication was also made using continuous exposure for 16 days in waterborne ethanol (0.5%) and assessing anxiety‐like behavior in the light/dark test after 60 min withdrawal. Withdrawal was shown to reduce preference for darkness, consistent with decreased anxiety, but to increase risk assessment, consistent with increased anxiety. Animals were also subjected to the withdrawal protocol and injected with pilocarpine in a sub‐convulsive dose to assess susceptibility to epileptic seizure‐like behavior. The protocol was sufficient to increase susceptibility to epileptic seizure‐like behavior in animals exposed to ethanol. Finally, withdrawal also decreased catalase activity in the brain, but not in the head kidney, suggesting mechanisms associated with the behavioral effects of ethanol withdrawal. HighlightsDiscrepancies in the literature on ethanol withdrawal in zebrafish modelsA metanalysis suggests ethanol concentration during exposure and exposure duration to be the main sources of variation.Ethanol withdrawal after exposure for 16 days decreased dark preference, but increased risk assessment.Withdrawal increased susceptibility to pilocarpine‐induced seizures.Withdrawal decreased catalase activity in the brain.

Keywords: ethanol withdrawal; anxiety; exposure; effects ethanol; withdrawal; withdrawal zebrafish

Journal Title: Pharmacology Biochemistry and Behavior
Year Published: 2018

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