S30. SCHIZOPHRENIA IN A FISH: EFFECTS OF NMDA ANTAGONISM ON LOCOMOTOR BEHAVIOR AND SOCIAL INTERACTION IN ZEBRAFISH

Background Applying cross-species approaches in animal preclinical studies of psychiatric disorders can minimize the overinterpretations often generated using specific strains or species in animal models of human conditions. Zebrafish is a model organism widely used in neuroscience research as an alternative to rodents, but protocols relevant to the symptoms and neurobiology of schizophrenia have not been fully established and validated in this species. MK-801, an NMDA receptor antagonist, is frequently used to recapitulate schizophrenia symptoms in rodent models. We thus aimed to evaluate the effects of a concentration curve of MK-801 on locomotor activity, social interaction, and neurochemical parameters related to oxidative stress in adult zebrafish. Methods Wild-type male and female zebrafish (50:50 ratio) were randomly allocated to 4 groups: control; 1 µM MK-801; 5 µM MK-801 or 10 µM MK-801 (n = 12). In the locomotor activity test animals were individually and sequentially placed in (1) a beaker with 200 mL of water for 20 min, (2) test aquarium for 30 min to assess basal locomotor activity, (3) beaker with water or MK-801 at the different concentrations for 20 min, and (4) test aquarium for 60 min. Locomotor and exploratory parameters (total distance traveled and upper zone time) were automatically analyzed using ANY-Maze software. In the social interaction test animals were individually exposed to water or MK-801 for 20 min and then placed for 7 min in a tank flanked by two identical tanks either empty or containing 10 zebrafish serving as social stimuli. Distance traveled was automatically tracked while social interaction time was manually and blindly scored using Boris software; only the last 5 minutes were analyzed. Oxidative damage in the brain was assessed by the levels of thiobarbituric acid reactive substances (TBARS). Data were analyzed by ANOVA followed by Tukey post hoc test. Results Exposure to 5 µM MK-801 decreased the total distance traveled in the locomotor activity test. In the social interaction test, exposure to 5 and 10 µM MK-801 significantly increased the total distance traveled while reduced the time of social interaction with the stimulus animals. No differences in TBARS levels were found between the groups. Discussion Unlike what is observed in rodents after MK-801 administration, zebrafish did not show hyperlocomotion at the concentrations tested. Other studies point to the context-dependent effect of this drug, as an increase in locomotor activity is only observed when animals are tested in a novel environment. In the social interaction test, on the other hand, animals were tested in a novel context with social stimulus and zebrafish exhibited hyperlocomotion and decreased social interaction, similar to what is observed in rodents. In contrast to chronic animal models and patients with schizophrenia, there were no differences in TBARS levels after acute exposure to MK-801. These preliminary results reinforce that zebrafish is an alternative model organism useful to the study of psychotic disorders. More behavioral and biochemical tests are needed to achieve reproducible tests and models to study multiple schizophrenia domains in zebrafish.

Galanthum nivalis Extract is Neurologically Active and Improves Anxiety and Social Interactions in Mesocricetus auratus

Background: Galanthum nivalis has been used throughout history for its medicinal properties. Although traditionally used as an antidote to poison, G. nivalis has also recently been found to have effects in neurological conditions such as Alzheimer’s Disease and mild cognitive impairment. Recent studies also suggest that it may have neurological activity that may be beneficial for psychiatric and neurological disorders like anxiety. </P><P> Objective: This study aimed to assess the neurological activity of G. nivalis extract using a behavioral test of anxiety-like behavior in Syrian hamsters. Methods: G. nivalis extract was administered daily to hamsters while undergoing a semi-naturalistic version of the open field test to assess anxiety. Hamsters were video recorded during their natural active times beginning an hour before and ending an hour after lights-on and lights-off. Free roaming behaviors were scored in a 2 x 4 m open pen with enrichment objects for hamsters to interact with. After 10 days, hamsters were subjected to a social interaction test with a novel conspecific. Results: Hamsters receiving G. nivalis extract showed increased time that was spent free-roaming and a greater proportion of that time was spent moving. They also spent more time interacting with enrichment objects in the open pen. The social interaction test showed that hamsters receiving G. nivalis extract spent more time playing with a novel conspecific. Conclusion: G. nivalis extract is a neurologically active natural product with behaviorally relevant effects. It improved anxiety-like behavior in hamsters, as evidenced by increased time free roaming, moving, and interacting with objects, while improving social interactions.

A new model as an early life manipulation: Fake mother

IntroductionEarly life stressful events cause long-term neural changes that are associated with psychiatric disorders.ObjectiveEarly life manipulations focus on commonly the impact of remaining separate from the mother in a specific period of time. The maternal odor is required for pups to approach the mother for nursing. What happens when there is a mother that smell like a real mother but does not take care her own pups?AimTo investigate the fake mother effects on adult rat's behavioral changes, NMDR2B protein level changes in prefrontal cortex and hippocampus.MethodsWistar rats were used. Fake mother (n:13), early handling (n:12), maternal separation (n:14) and control (n:12) were the study groups. A fake mother is an object that smells like a real dam. When the real mother is separated from own pups fake mother stays with the pups for an hour. Manipulations were made during the postnatal first 14 days. Behavioral tests (social interaction test, elevated plus maze, novel object recognition test) were made between postnatal 62 and 78 days. NMDAR2B protein levels in prefrontal cortex and hippocampus were evaluated by using ELISA at postnatal 78 days.ResultsIn social interaction test, fake mother group exhibited less social behavior and more aggressive behavior than the other groups. Their long-term memory functions were the lowest. NMDAR2B protein levels in the hippocampus increased in rats that exposed to early stressful life events.ConclusionThese results support that being raised by fake mother increases aggressive behavior and decrease social behavior in adulthood.Disclosure of interestThe authors have not supplied their declaration of competing interest.