Naltrexone Alters Neurochemical and Behavioral Parameters in a Zebrafish Model of Repeated Alcohol Exposure

Abstract

Between the neurotransmission systems modulated by alcohol, the opioid system has been receiving attention in studies that seek to understand its relationship to the effects of addictive substances and different neuropsychiatric disorders. The use of naltrexone stands out in determining the mechanisms of the opioid system, as it acts as an opioid antagonist and consequently generates neurochemical responses. This study aimed to evaluate the pharmacological modulation of opioids on behavioral and neurobiological aspects in adult zebrafish submitted to the protocol of repeated exposure to ethanol and treated with naltrexone. Opioid modulation using naltrexone has been shown to modulate anxiety-like behavior, presenting anxiolytic properties in isolation, in addition to reversing the anxiogenic effect of ethanol through the Novel tank and Light/dark test. Naltrexone increased serotonin and dopamine levels, while ethanol antagonized these effects. In contrast, the interaction between ethanol and naltrexone raised noradrenaline levels. Naltrexone altered glutamate levels, however, ethanol reversed it. Ethanol acted on glutamate transporters increasing their activities, while naltrexone treatment reduced activities. No significant results were found in the pro-oxidant parameters, however, ethanol reduced SOD activity while naltrexone reversed. The same occurred in CAT activity. Also, naltrexone up-regulated the expression of genes related to the dopaminergic, glutamatergic, and opioid systems. The genes used as markers of the inflammatory process and glial activity were modulated by ethanol and together with naltrexone, respectively. Taken together, our findings reinforce the importance of opioid signaling on biochemical and molecular bases related to neuropsychiatric behaviors and diseases, such as anxiety and substance dependence.