Hyperprolinemia is an inherited disorder of
proline metabolism and patients affected by this disease may present
neurological manifestations, including
seizures and
cognitive dysfunctions. Moreover, an association between adulthood
schizoaffective disorders and moderate hyperprolinemia has been reported. However, the mechanisms underlying these behavioral phenotypes still remain unclear. In the present study, we investigated the effect of
proline treatments on behavioral parameters in zebrafish, such as locomotor activity, anxiety, and social interaction. Adult zebrafish (Danio rerio) were exposed to
proline (1.5 and 3.0 mM) during 1h or 7 days (short- or long-term treatments, respectively). Short-term
proline exposure did not promote significant changes on the behavioral parameters observed. Long-term exposure at 1.5 mM
proline significantly increased the number of line crossing (47%), the total distance (29%), and the mean speed (33%) when compared to control group. A significant increase in the time spent in the upper portion of the test tank was also observed after this treatment (91%), which may be interpreted as an
indicator of
anxiolytic behavior.
Proline at 1.5 mM also induced social interaction impairment (78%), when compared to the untreated group after long-term treatment. Moreover, these
proline-induced behavioral changes in zebrafish were completely reversed by acute administration of an atypical
antipsychotic drug (
sulpiride), but not by a typical (
haloperidol). These findings demonstrate that
proline is able to induce
schizophrenia-like symptoms in zebrafish, which reinforce the use of this species as a complementary vertebrate model for studying behavioral phenotypes associated with neurological dysfunctions characteristic of
metabolic diseases.