Physical exercise prevents behavioral alterations in a reserpine-treated zebrafish: A putative depression model.

Major depressive disorder (MDD) has increasingly reached the world population with an expressive increase in recent years due to the COVID-19 pandemic. Here we used adult zebrafish (Danio rerio) as a model to verify the effects of reserpine on behavior and neurotransmitter levels. We observed an increase in the immobile time and time spent in the bottom zone of the tank in reserpine-exposed animals. The results demonstrated a decrease in distance traveled and velocity. Reserpine exposure did not induce changes in memory and social interaction compared to the control group. We also evaluated the influence of exposure to fluoxetine, a well-known antidepressant, on the behavior of reserpine-exposed animals. We observed a reversal of behavioral alterations caused by reserpine. To verify whether behavioral alterations in the putative depression model induced by reserpine could be prevented, the animals were subjected to physical exercise for 6 weeks. The results showed a protective effect of the physical exercise against the behavioral changes caused by reserpine in zebrafish. In addition, we observed a reduction in dopamine and serotonin levels and an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the brain. Physical exercise was able to prevent the changes in dopamine and serotonin levels, reinforcing that the preventive effect promoted by physical exercise is related to the modulation of neurotransmitter levels. Our findings showed that reserpine was effective in the induction of a putative depression model in zebrafish and that physical exercise may be an alternative to prevent the effects induced by reserpine.

Standardizing Zebrafish Behavioral Paradigms Across Life Stages: An Effort Towards Translational Pharmacology.

Zebrafish is a prominent vertebrate model, with many of its advantages related to its development, life cycle, and translational ability. While a great number of behavioral phenotypes and tasks to evaluate them are available, longitudinal studies across zebrafish life stages are scarce and made challenging because of the differences between protocols and endpoints assessed at each life stage. In this mini review, we highlight the relevance that longitudinal studies could have for neurobehavioral pharmacology using this model. We also present possible strategies to standardize behavior endpoints in domains related to human diseases throughout the life cycle, especially between larvae and adult fish. Furthermore, we discuss the remaining difficulties of these analyses and explore future advances needed to bridge this knowledge gap.

Antibiotic drugs alter zebrafish behavior.

Antibiotics are widely used drugs in human and veterinary health as well as in the food industry. The majority of these compounds are, however, excreted unchanged and found as contaminants in water bodies. Although the toxicity of these drugs was previously studied in aquatic organisms, the behavioral effects of these pollutants have not been fully explored. Here we exposed adult zebrafish to environmentally relevant concentrations of different classes of antibiotics (Chlortetracycline, Ciprofloxacin, and Ceftazidime) and assessed zebrafish exploratory, cognitive, aggressive, and social behaviors. Ciprofloxacin, Chlortetracycline, and Ceftazidime exposure induced hyperlocomotion, which was characterized by an increase in the distance traveled in zebrafish. These antibiotics promoted cognitive decline and exacerbated aggressive behavior. In summary, this study shows that antibiotic contamination may impact zebrafish behavior in a short-time manner.

Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish.

The mTORC1 complex integrates different inputs from intracellular and extracellular signals to control various cellular processes. Therefore, any disruption in the mTORC1 pathway could promote different neurological disorders. mTORC1 overactivation has been verified in different genetic and acquired epilepsy animal models. Therefore, inhibitors of this complex could have both antiepileptogenic and antiseizure effects. In our study, we investigated the effects of rapamycin pretreatment on pentylenetetrazole (PTZ)-induced seizures in zebrafish. Our results have shown that the latency to reach the tonic-clonic stage (stage III) of progressive behavioral alterations shown during PTZ-induced seizures was prolonged in larval (7days post fertilization, 7dpf), juvenile (45days post fertilization, 45dpf) and adult (6-8months) zebrafish after pretreatment with rapamycin. Furthermore, rapamycin pretreatment did not alter the locomotor activity in zebrafish. Therefore, the results obtained in our study indicate that rapamycin pretreatment is an important mechanism to control the progress of seizures in zebrafish throughout different developmental stages (larval, juvenile, and adult). Taken as a whole, our data support that rapamycin has immediate antiseizure effects and could be a potential alternative therapy for seizure control in epilepsy.