The results of our light and dark test showed that light attenuated activity, whereas darkness facilitated activity in normal zebrafish. However, when exposed to haloperidol, subjects had no reaction to light or dark. At higher haloperidol concentrations (1, 5, and 10 mg/L), we observed significant decreases in locomotor activity but no effect on heart rate. Given this minimal influence, we concluded that haloperidol does not strongly affect cardiopulmonary functions. Although this result implied that automatic nerves are not associated with the attenuation of locomotion in zebrafish, we have little insight regarding the involvement of α1 adrenergic receptors. We found no signs of rhabdomyolysis and vertebral deformation. These findings suggest that haloperidol has distinct advantages over psychotomimetic drugs (e.g., methamphetamine) and psychoactive designer drugs (e.g., 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl) ethanamine), which induce complications like rhabdomyolysis . These complications are associated with hyperactivity or hyperthermia, so antipsychotics that induce hypoactivity and immobilization are unlikely to have similar side effects.
Regarding the number of repetitions of light stimulation, the data were unified with little variation, especially in the 3rd, 4th, and 5th light and dark bands, but the data were not stable at the 1st, 2nd, and 6th times. Therefore, it is can be inferred that the data of the 3rd, 4th, and 5th times show the significant difference between the haloperidol groups and the control group. This is because the 1st and 2nd times vary owing to individual differences between groups, but the behavioral patterns are unified because the fish are acclimatized and their behavior is stable in the 3rd and subsequent times. In addition, as the behavior becomes unstable again from the 6th time onward, the reliability of the data after that is expected to decrease. Therefore, it is assumed that the most efficient and reliable light stimulation is in the 3rd, 4th, and 5th light stimulations which constitute six consecutive periods.
What is noteworthy in this result is that not only does the activity of the dark band gradually decrease according to the concentration gradient when comparing the distance traveled between the light band and the dark band, but also the activity of the dark band decreases to the same level as that of the light band at 5 mg/L. Furthermore, it is surprising that the phenomenon of the reversal of the amount of activity in the light and dark bands at 10 mg/L is confirmed.
This result clarifies not only the catalepsy symptoms of decreased activity and responsiveness to light stimulus but also unexpected behavior patterns as a result of increased haloperidol concentration. Importantly, this screening may change the current perception of haloperidol.
The low toxicity of haloperidol makes it less of a priority in psychiatric treatment research than other psychomimetic drugs because it is rarely linked to sudden deaths in conditions such as dementia . However, some research suggests that the dangers of haloperidol may be underestimated. Schizophrenic inpatients under antipsychotic monotherapy had significantly worse performance in a driving simulator when they were treated with haloperidol than with other antipsychotic drugs . However, when traffic accidents are associated with schizophrenia and antipsychotic drug treatments, driving dysfunctions are typically only attributed to illness-induced catalepsy. Our study suggests that antipsychotic drugs like haloperidol could cause exogenous catalepsy along with the endogenous catalepsy from schizophrenia, both of which could then combine to result in serious physical dysfunctions. Thus, we recommend that psychiatrists perform inquests into causes of driving-related accidents until the presence or absence of any correlation between drug intake and catalepsy is firmly established.
In summary, we demonstrated that the light and dark test is an appropriate substitute for the bar test in terms of evaluating catalepsy-like immobilization in zebrafish. Additionally, we demonstrated that haloperidol only temporarily induced the locomotive disorders, supporting previous findings . Moreover, haloperidol treatment had minimal effect on heart rate or morphology. Our study has important implications for the persistence of drug complications. The results of our study suggest that the zebrafish model could advance considerably and become useful in the behavioral screening for haloperidol-induced catalepsy.