TY - CHAP

T1 - Antipsychotic drug levomepromazine action on adult zebrafish behavior in novel tank test

AU - Demin, K.A.

AU - Kalueff, A.V.

PY - 2018/7/20

Y1 - 2018/7/20

N2 - Schizophrenia is an extremely debilitating psychiatric disorder. Levomepromazine is a neuroleptic drug that can be used for manic phases of bipolar disorder, and is also widely used in palliative care. However, little is known about its efficacy for schizophrenia. Mounting evidence suggests the use of zebrafish in antipsychotic drugs screening due to its high genetic and physiological homology to humans. Here we apply zebrafish novel tank test to study the effects of levomepromazine on their locomotion and behavior. Behavioral testing was performed in adult wild-type outbredshort-fin zebrafish between 11.00 and 17.00 h, using tanks (20x20x5 cm) with water adjusted to the holding room temperature, to assess zebrafish behavior. Prior to testing, fish were preexposed in a 0.5-L plastic beaker for 20 min to either drug-treated or drug-free water. For experiment, fish were randomly divided into 3 groups (n=9-10): drug-free control and fish preexposed to 25 mg/L or 50 mg/L of levomepromazine. Doses were chosen based on pilot studies in which higher (100 mg/L) resulted in ataxic responses. Zebrafish behavior was recorded on webcam and then processed in Noldus EthoVision XT 11.5. Was studied such behavioral endpoints as distance moved (cm), moving and not moving durations (s), time spent in the top part of tank (s) and number of transitions from bottom to top (n), absolute mean meandering (deg/cm). For statistical evaluation was used Kruskal-Wallis test with posthoc Dunn’s test for pair comparisons of statistically significant KW data. Data is represented as Mean±SEM. Overall, levomepromazine exposure alters zebrafish behavior, decreasing time spent moving (p<0.05 for KW comparison, p>0.05 for 25 mg/L and p<0.05 for 50 mg/L in Dunn’s test vs. control; 253.590±12.5572s, 196,462±21.7011s and 158.096±32.158 respectively), increasing time spent not moving (p<0.05 for KW comparison, p>0.05 for 25 mg/L and p<0.05 for 50 mg/L in Dunn’s test vs. control; 43.833±12.4763, 102.192±21.8682, 135.638±29.340 respectively), increasing absolute mean meandering (p<0.01 for KW comparison, p>0.05 for 25 mg/L and p<0.01 for 50 mg/L in Dunn’s test vs. control; 305.994±126.6485, 1177.727±380.0390, 7373.960±2977.579 respectively) and decreasing number of zone transitions (p<0.001 for KW comparison, p<0.001 for 25 mg/L and p<0.05 for 50 mg/L in Dunn’s test vs. control; 18.333±3.1091, 2.700±0.8699, 5.800±2.107 respectively). There was no difference in distance moved and time spent in the top half of tank (p>0.05). Taken together, this data suggests a mild hypolocomotor profile. Interestingly, giving changes in zone transitions and time spent in top that occurred in different directions compared to control, lower doses of the drug also seem to produce anxiolytic effect, which becomes anxiogenic in higher dose (182.8054±11.44136, 227.0210±22.62603, 136.9333±35,42235 for control, 25 and 50 mg/L doses.

AB - Schizophrenia is an extremely debilitating psychiatric disorder. Levomepromazine is a neuroleptic drug that can be used for manic phases of bipolar disorder, and is also widely used in palliative care. However, little is known about its efficacy for schizophrenia. Mounting evidence suggests the use of zebrafish in antipsychotic drugs screening due to its high genetic and physiological homology to humans. Here we apply zebrafish novel tank test to study the effects of levomepromazine on their locomotion and behavior. Behavioral testing was performed in adult wild-type outbredshort-fin zebrafish between 11.00 and 17.00 h, using tanks (20x20x5 cm) with water adjusted to the holding room temperature, to assess zebrafish behavior. Prior to testing, fish were preexposed in a 0.5-L plastic beaker for 20 min to either drug-treated or drug-free water. For experiment, fish were randomly divided into 3 groups (n=9-10): drug-free control and fish preexposed to 25 mg/L or 50 mg/L of levomepromazine. Doses were chosen based on pilot studies in which higher (100 mg/L) resulted in ataxic responses. Zebrafish behavior was recorded on webcam and then processed in Noldus EthoVision XT 11.5. Was studied such behavioral endpoints as distance moved (cm), moving and not moving durations (s), time spent in the top part of tank (s) and number of transitions from bottom to top (n), absolute mean meandering (deg/cm). For statistical evaluation was used Kruskal-Wallis test with posthoc Dunn’s test for pair comparisons of statistically significant KW data. Data is represented as Mean±SEM. Overall, levomepromazine exposure alters zebrafish behavior, decreasing time spent moving (p<0.05 for KW comparison, p>0.05 for 25 mg/L and p<0.05 for 50 mg/L in Dunn’s test vs. control; 253.590±12.5572s, 196,462±21.7011s and 158.096±32.158 respectively), increasing time spent not moving (p<0.05 for KW comparison, p>0.05 for 25 mg/L and p<0.05 for 50 mg/L in Dunn’s test vs. control; 43.833±12.4763, 102.192±21.8682, 135.638±29.340 respectively), increasing absolute mean meandering (p<0.01 for KW comparison, p>0.05 for 25 mg/L and p<0.01 for 50 mg/L in Dunn’s test vs. control; 305.994±126.6485, 1177.727±380.0390, 7373.960±2977.579 respectively) and decreasing number of zone transitions (p<0.001 for KW comparison, p<0.001 for 25 mg/L and p<0.05 for 50 mg/L in Dunn’s test vs. control; 18.333±3.1091, 2.700±0.8699, 5.800±2.107 respectively). There was no difference in distance moved and time spent in the top half of tank (p>0.05). Taken together, this data suggests a mild hypolocomotor profile. Interestingly, giving changes in zone transitions and time spent in top that occurred in different directions compared to control, lower doses of the drug also seem to produce anxiolytic effect, which becomes anxiogenic in higher dose (182.8054±11.44136, 227.0210±22.62603, 136.9333±35,42235 for control, 25 and 50 mg/L doses.

UR - https://events.spbu.ru/eventsContent/events/2018/ITBM/%D0%A1%D0%91%D0%9E%D0%A0%D0%9D%D0%98%D0%9A_%D0%A2%D0%B5%D0%B7%D0%B8%D1%81%D0%BE%D0%B2%20%D0%98%D0%A2%D0%91%D0%9C_2507.pdf

M3 - Other chapter contribution

SP - 69

BT - Актуальные проблемы трансляционной биомедицины - 2018

PB - Издательство Санкт-Петербургского университета

CY - СПб.

T2 - 4-я ежегодная конференция Института Трансляционной <br/>биомедицины СПбГУ (ИТБМ СПбГУ) «Актуальные проблемы трансляционной биомедицины - 2018»

Y2 - 20 July 2018 through 22 July 2018

ER -