Background: Rotenone (ROT) is currently being used in various research fields, especially neuroscience. Separated from other neurotoxins, ROT induces a Parkinson’s disease (PD)-related phenotype that mimics the associated clinical spectrum by directly entering the central nervous system (CNS). It easily crosses through the blood−brain barrier (BBB) and accumulates in mitochondria. Unfortunately, most of the existing data focus on locomotion. This is why the present study aimed to bring novel evidence on how ROT alone or in combination with different potential ant(agonists) might influence the social and aggressive behavior using the counterclockwise rotation as a neurological pointer. Material and Methods: Thus, we exposed zebrafish to ROT—2.5 µg/L, valproic acid (VPA)—0.5 mg/mL, anti-parkinsonian drugs (LEV/CARB)—250 mg + 25 mg, and probiotics (PROBIO)—3 g for 32 days by assessing the anti-social profile and mirror tests and counterclockwise rotation every 4 days to avoid chronic stress. Results: We observed an abnormal pattern in the counterclockwise rotation only in the (a) CONTROL, (c) LEV/CARB, and (d) PROBIO groups, from both the top and side views, this indicating a reaction to medication and supplements administered or a normal intrinsic feature due to high levels of stress/anxiety (p < 0.05). Four out of eight studied groups—(b) VPA, (c) LEV/CARB, (e) ROT, and (f) ROT + VPA—displayed an impaired, often antithetical behavior demonstrated by long periods of time on distinct days spent on the right and the central arm (p < 0.05, 0.005, and 0.0005). Interestingly, groups (d) PROBIO, (g) ROT + LEV/CARB, and (h) ROT + PROBIO registered fluctuations but not significant ones in contrast with the above groups (p > 0.05). Except for groups (a) CONTROL and (d) PROBIO, where a normalized trend in terms of behavior was noted, the rest of the experimental groups exhibited exacerbated levels of aggression (p < 0.05, 0.005, and 0.001) not only near the mirror but as an overall reaction (p < 0.05, 0.005, and 0.001). Conclusions: The (d) PROBIO group showed a significant improvement compared with (b) VPA, (c) LEV/CARB, and ROT-treated zebrafish (e−h). Independently of the aggressive-like reactions and fluctuations among the testing day(s) and groups, ROT disrupted the social behavior, while VPA promoted a specific typology in contrast with LEV/CARB.
Keywords: Danio rerio; Parkinson’s disease; aggressivity; anti-social; counterclockwise rotation; rotenone; zebrafish.