EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S1 Supplementary data to: THE ROLE OF CA1 CB1 RECEPTORS ON LITHIUM-INDUCED SPATIAL MEMORY IMPAIRMENT IN RATS Salar Vaseghi1, Vahab Babapour2, Mohammad Nasehi3*, Mohammad-Reza Zarrindast4,5,6 1 Department of Physiology, Faculty of Veterinary Science, Science and Research Branch, Islamic Azad University, Tehran, Iran 2 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran 3 Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran 4 Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 5 Institute for Cognitive Science Studies (ICSS), Tehran, Iran 6 Department of Neuroendocrinology, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran * Corresponding author: M. Nasehi (Nasehi@iricss.org; Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran). P.O. Box 13145-784, Tel: +9821-99881118-20, Fax: +9821-99881117 http://dx.doi.org/10.17179/excli2018-1511 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S2 Raw Data Escape latency (Time): sec Traveled distance: cm Swimming speed: cm/sec Trials Supplementary Tables “1” for Figure 1: Effects of ACPA on spatial learning and swimming speed. Four groups of eight animals received pre-training intra-CA1 administration of saline (1 µl/rat) or different doses of ACPA (0.001, 0.01 and 1 µg/rat). 5 min after the injection animals were trained in MWM apparatus. EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S3 Figure 1A: Effects of ACPA on escape latency (Time) Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 49 39 27 22 16 12 7 6 2 46 35 29 17 14 11 7 7 3 44 36 26 19 14 10 6 6 4 47 40 30 21 19 12 8 8 5 60 47 31 24 18 14 7 9 6 50 42 29 19 15 10 9 7 7 60 49 33 25 17 12 7 6 8 52 41 27 22 18 11 8 9 Figure 1A: Effects of ACPA on escape latency (Time): Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 53 44 32 29 27 22 19 2 51 42 40 33 31 26 20 22 3 60 46 38 32 28 22 22 19 4 56 60 41 36 29 25 22 18 5 47 39 33 25 26 28 21 18 6 42 38 37 33 30 27 25 20 7 51 43 40 30 28 25 27 19 8 60 60 40 32 26 29 25 17 Figure 1A: Effects of ACPA on escape latency (Time): ACPA 0.001 µg/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 52 46 35 37 27 24 21 2 56 60 42 40 36 33 22 26 3 60 51 40 43 33 35 31 28 4 60 60 53 48 43 33 29 25 5 47 40 32 26 27 22 18 19 6 42 60 50 36 31 22 28 24 7 50 42 35 30 29 24 19 20 8 60 49 45 39 33 26 23 23 Figure 1A: Effects of ACPA on escape latency (Time): ACPA 0.01 µg/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 52 46 35 32 24 22 24 2 60 49 39 30 29 30 26 25 3 60 60 41 40 35 33 26 29 4 55 60 37 40 35 27 24 26 5 45 52 38 29 40 21 20 18 6 47 43 41 36 33 27 24 21 7 52 60 51 41 36 31 29 25 8 60 60 48 38 39 33 24 26 Figure 1A: Effects of ACPA on escape latency (Time): ACPA 1 µg/rat EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S4 Figure 1B: Effects of ACPA on traveled distance Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1467 1210 891 756 535 387 232 222 2 1398 1110 943 589 422 349 250 241 3 1366 1154 852 652 431 316 212 209 4 1424 1245 989 737 666 366 287 291 5 1767 1412 1042 792 623 404 230 287 6 1571 1291 958 670 452 296 302 245 7 1788 1491 1123 842 587 376 240 223 8 1612 1287 876 755 617 345 292 310 Figure 1B: Effects of ACPA on traveled distance: Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1744 1622 1346 1067 930 875 729 666 2 1591 1326 1261 1081 1008 845 701 724 3 1771 1404 1167 1051 879 699 731 678 4 1690 1786 1255 1131 919 804 702 621 5 1414 1225 1089 825 845 896 691 634 6 1311 1187 1125 1090 955 866 798 689 7 1579 1341 1255 977 888 810 845 633 8 1759 1764 1241 1025 843 900 808 591 Figure 1B: Effects of ACPA on traveled distance: ACPA 0.001 µg/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1755 1588 1378 1091 1100 874 790 732 2 1677 1791 1333 1269 1102 1043 701 878 3 1773 1511 1246 1378 1003 1123 994 915 4 1821 1794 1619 1498 1389 1089 946 818 5 1447 1245 988 822 829 732 612 698 6 1331 1811 1525 1200 979 712 911 803 7 1566 1347 1145 989 941 789 655 707 8 1721 1498 1409 1241 1002 828 738 776 Figure 1B: Effects of ACPA on traveled distance: ACPA 0.01 µg/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1744 1618 1411 1111 1077 833 746 795 2 1812 1522 1158 978 941 965 865 805 3 1789 1750 1278 1288 1109 1100 808 951 4 1671 1733 1155 1259 1135 904 798 869 5 1393 1605 1201 944 1300 733 725 635 6 1423 1406 1324 1189 1005 861 778 745 7 1599 1772 1597 1265 1120 1001 977 810 8 1753 1824 1510 1178 1172 1084 800 867 Figure 1B: Effects of ACPA on traveled distance: ACPA 1 µg/rat EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S5 Figure 1C: Effects of ACPA on swimming speed Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.93 31.02 33.00 34.36 33.43 32.25 33.14 37.00 2 30.39 31.71 32.51 34.64 30.14 31.72 35.71 34.42 3 31.04 32.05 32.76 34.31 30.78 31.60 35.33 34.83 4 30.29 31.12 32.96 35.09 35.05 30.50 35.87 36.37 5 29.45 30.04 33.61 33.00 34.61 28.85 32.85 31.88 6 31.42 30.73 33.03 35.26 30.13 29.60 33.55 35.00 7 29.80 30.42 34.03 33.68 34.52 31.33 34.28 37.16 8 31.00 31.39 32.44 34.31 34.27 31.36 36.50 34.44 Figure 1C: Effects of ACPA on swimming speed: Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.06 30.60 30.59 33.34 32.06 32.40 33.13 35.05 2 31.19 31.57 31.52 32.75 32.51 32.50 35.05 32.90 3 29.51 30.52 30.71 32.84 31.39 31.77 33.22 35.68 4 30.17 29.76 30.60 31.41 31.68 32.16 31.90 34.50 5 30.08 31.41 33.00 33.00 32.50 32.00 32.90 35.22 6 31.21 31.22 30.40 33.03 31.83 32.07 31.92 34.45 7 30.96 31.18 31.37 32.56 31.71 32.40 31.29 33.31 8 29.31 29.40 31.02 32.03 32.42 31.03 32.32 34.76 Fiure 1C: Effects of ACPA on swimming speed: ACPA 0.001 µg/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.25 30.53 29.95 31.17 29.72 32.37 32.91 34.85 2 29.94 29.85 31.73 31.72 30.61 31.60 31.86 33.76 3 29.55 29.62 31.15 32.04 30.39 32.08 32.06 32.67 4 30.35 29.90 30.54 31.20 32.30 33.00 32.62 32.72 5 30.78 31.12 30.87 31.61 30.70 33.27 34.00 36.73 6 31.69 30.18 30.50 33.33 31.58 32.36 32.53 33.45 7 31.32 32.07 32.71 32.96 32.44 32.87 34.47 35.35 8 28.68 30.57 31.31 31.82 30.36 31.84 32.08 33.73 Figure 1C: Effects of ACPA on swimming speed: ACPA 0.01 µg/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.06 31.11 30.67 31.74 33.65 34.70 33.90 33.12 2 30.20 31.06 29.69 32.60 32.44 32.16 33.26 32.20 3 29.81 29.16 31.17 32.20 31.68 33.33 31.07 32.79 4 30.38 28.88 31.21 31.47 32.42 33.48 33.25 33.42 5 30.95 30.86 31.60 32.55 32.50 34.90 36.25 35.27 6 30.27 32.69 32.29 33.02 30.45 31.88 32.41 35.47 7 30.75 29.53 31.31 30.85 31.11 32.29 33.68 32.40 8 29.21 30.40 31.45 31.00 30.05 32.84 33.33 33.34 Figure 1C: Effects of ACPA on swimming speed: ACPA 1 µg/rat EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S6 Raw Data Escape latency (Time): sec Traveled distance: cm Swimming speed: cm/sec Trials Supplementary Tables “2” for Figure 2: Effects of AM251 on spatial learning and swimming speed. Four groups of eight ani- mals received pre-training intra-CA1 administration of saline (1 µl/rat) or different doses of AM251 (1, 10 and 100 ng/rat). 5 min after the injection animals were trained in MWM apparatus. EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S7 Figure 2A: Effects of AM251 on escape latency (Time) Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 49 39 27 22 16 12 7 6 2 46 35 29 17 14 11 7 7 3 44 36 26 19 14 10 6 6 4 47 40 30 21 19 12 8 8 5 60 47 31 24 18 14 7 9 6 50 42 29 19 15 10 9 7 7 60 49 33 25 17 12 7 6 8 52 41 27 22 18 11 8 9 Figure 2A: Effects of AM251 on escape latency (Time): Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 49 53 39 33 30 26 18 17 2 60 52 38 35 26 22 21 20 3 52 51 42 31 24 29 22 21 4 52 37 32 25 26 28 24 18 5 60 42 35 32 32 24 19 17 6 53 44 39 31 29 22 24 18 7 60 41 40 27 29 29 20 15 8 52 45 41 36 32 24 25 19 Figure 2A: Effects of AM251 on escape latency (Time): AM251 1 ng/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 53 42 32 29 25 26 20 2 53 60 52 35 19 22 23 15 3 60 53 45 29 22 24 18 14 4 60 46 42 25 27 19 21 22 5 45 43 38 30 32 28 27 18 6 55 45 42 39 34 25 19 20 7 60 53 42 37 29 26 22 16 8 51 46 37 41 31 25 29 20 Figure 2A: Effects of AM251 on escape latency (Time): AM251 10 ng/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 43 44 21 22 18 22 19 2 58 51 43 27 29 25 23 21 3 51 45 35 38 35 23 25 16 4 60 60 45 35 30 20 23 15 5 60 58 44 35 23 23 20 19 6 58 44 47 42 29 21 19 20 7 48 49 34 37 24 30 25 21 8 51 60 47 36 40 26 29 18 Figure 2A: Effects of AM251 on escape latency (Time): AM251 100 ng/rat EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S8 Figure 2B: Effects of AM251 on traveled distance Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1467 1210 891 756 535 387 232 222 2 1398 1110 943 589 422 349 250 241 3 1366 1154 852 652 431 316 212 209 4 1424 1245 989 737 666 366 287 291 5 1767 1412 1042 792 623 404 230 287 6 1571 1291 958 670 452 296 302 245 7 1788 1491 1123 842 587 376 240 223 8 1612 1287 876 755 617 345 292 310 Figure 2B: Effects of AM251 on traveled distance: Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1433 1645 1214 1091 969 850 590 584 2 1741 1605 1184 1144 861 712 694 670 3 1600 1567 1311 978 790 933 731 702 4 1589 1154 1084 821 856 893 761 603 5 1756 1290 1092 1010 1041 778 648 562 6 1626 1354 1178 966 926 742 795 584 7 1760 1245 1234 900 911 949 681 438 8 1617 1337 1228 1187 1014 782 784 610 Figure 2B: Effects of AM251 on traveled distance: AM251 1 ng/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1757 1674 1265 1032 943 768 806 700 2 1598 1795 1632 1110 621 704 745 422 3 1734 1654 1322 922 723 758 567 387 4 1765 1362 1241 823 878 643 698 745 5 1310 1256 1146 974 1035 916 871 590 6 1622 1302 1255 1235 1099 777 620 679 7 1751 1641 1240 1189 926 789 732 541 8 1590 1345 1206 1214 981 762 951 688 Figure 2B: Effects of AM251 on traveled distance: AM251 10 ng/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1768 1278 1287 694 722 589 734 624 2 1761 1482 1284 809 879 814 758 685 3 1600 1332 1125 1220 1178 774 800 521 4 1805 1745 1325 1119 1001 701 734 487 5 1758 1702 1293 1141 750 742 671 642 6 1721 1298 1387 1254 941 690 612 685 7 1398 1444 1108 1178 731 967 820 720 8 1489 1764 1360 1125 1170 784 960 595 Figure 2B: Effects of AM251 on traveled distance: AM251 100 ng/rat EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S9 Figure 2C: Effects of AM251 on swimming speed Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.93 31.02 33.00 34.36 33.43 32.25 33.14 37.00 2 30.39 31.71 32.51 34.64 30.14 31.72 35.71 34.42 3 31.04 32.05 32.76 34.31 30.78 31.60 35.33 34.83 4 30.29 31.12 32.96 35.09 35.05 30.50 35.87 36.37 5 29.45 30.04 33.61 33.00 34.61 28.85 32.85 31.88 6 31.42 30.73 33.03 35.26 30.13 29.60 33.55 35.00 7 29.80 30.42 34.03 33.68 34.52 31.33 34.28 37.16 8 31.00 31.39 32.44 34.31 34.27 31.36 36.50 34.44 Figure 2C: Effects of AM251 on swimming speed: Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.24 31.03 31.12 33.06 32.30 32.69 32.77 34.35 2 29.01 30.86 31.15 32.68 33.11 32.36 33.04 33.50 3 30.76 30.72 31.21 31.54 32.91 32.17 33.22 33.42 4 30.55 31.18 33.87 32.84 32.92 31.89 31.70 33.50 5 29.26 30.71 31.20 31.56 32.53 32.41 34.10 33.05 6 30.67 30.77 30.20 31.16 31.93 33.72 33.12 32.44 7 29.33 30.36 30.85 33.33 31.41 32.72 34.05 29.20 8 31.09 29.71 29.95 32.97 31.68 32.58 31.36 32.10 Figure 2C: Effects of AM251 on swimming speed: AM251 1 ng/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.28 31.58 30.11 32.25 32.51 30.72 31.00 35.00 2 30.15 29.91 31.38 31.71 32.68 32.00 32.32 28.13 3 28.90 31.20 29.37 31.79 32.86 31.58 31.50 27.64 4 29.41 29.60 29.54 32.92 32.51 33.84 33.23 33.86 5 29.11 29.20 30.15 32.46 32.34 32.71 32.25 32.77 6 29.42 28.93 29.88 31.66 32.32 31.08 32.63 33.95 7 29.18 30.96 29.52 32.13 31.93 30.34 33.27 33.81 8 31.17 29.23 32.59 29.60 31.64 30.48 32.79 34.40 Figure 2C: Effects of AM251 on swimming speed: AM251 10 ng/rat Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.46 29.72 29.25 33.04 32.81 32.72 33.36 32.84 2 30.36 29.05 29.86 29.96 30.38 32.56 32.95 32.61 3 31.37 29.60 32.14 32.10 33.65 33.65 32.00 32.56 4 30.08 29.08 29.44 31.97 33.36 35.05 31.91 32.46 5 29.30 29.34 29.38 32.60 32.60 32.26 33.55 33.78 6 29.67 29.50 29.51 29.85 32.44 32.85 32.21 34.25 7 29.12 29.46 32.58 31.83 30.45 32.23 32.80 34.28 8 29.19 29.40 28.93 31.25 29.25 30.15 33.10 33.05 Figure 2C: Effects of AM251 on swimming speed: AM251 100 ng/rat EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S10 Raw Data Escape latency (Time): sec Traveled distance: cm Swimming speed: cm/sec Trials Supplementary Tables “3” for Figure 3: Effects of lithium, and interaction between cannabinoids and lithium on spatial learning and swimming speed. The animals received pre-training intraperitoneal administration of saline (1 ml/kg) or different doses of lithium (0.5, 1 and 5 mg/kg). 5 min after pervious injection the animals received lower dose of ACPA (0.001 µg/rat; four groups, eight rats in each group) or AM251 (1 ng/rat; four groups, eight rats in each group). EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S11 Figure 3A: Effects of Lithium on escape latency (Time) Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 49 39 27 22 16 12 7 6 2 46 35 29 17 14 11 7 7 3 44 36 26 19 14 10 6 6 4 47 40 30 21 19 12 8 8 5 60 47 31 24 18 14 7 9 6 50 42 29 19 15 10 9 7 7 60 49 33 25 17 12 7 6 8 52 41 27 22 18 11 8 9 Figure 3A: Effects of Lithium on escape latency (Time): Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 48 26 22 17 10 12 6 2 60 60 37 28 15 11 7 8 3 47 45 24 27 14 14 8 6 4 42 25 28 22 15 19 10 10 5 55 34 29 18 20 9 10 6 6 51 40 21 15 14 9 17 9 7 60 31 27 25 19 11 12 10 8 44 33 19 24 11 15 7 8 Figure 3A: Effects of Lithium on escape latency (Time): Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 51 31 27 21 11 6 9 2 53 60 27 21 23 14 7 11 3 45 34 29 19 23 8 8 6 4 60 39 33 20 15 14 12 5 5 60 50 27 14 11 16 13 6 6 56 37 42 28 22 11 9 11 7 41 44 31 22 19 9 14 9 8 43 57 35 17 21 14 12 10 Figure 3A: Effects of Lithium on escape latency (Time): Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 55 60 41 22 23 14 9 7 2 42 35 26 31 18 15 6 6 3 60 36 40 28 19 14 7 8 4 60 51 33 21 15 20 13 7 5 60 44 39 25 22 11 12 11 6 39 28 33 18 21 12 10 10 7 55 41 36 19 15 8 11 8 8 42 29 30 24 24 15 11 8 Figure 3A: Effects of Lithium on escape latency (Time): Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S12 Figure 3A: Effects of ACPA 0.001 µg/rat + Lithium on escape latency (Time) Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 53 44 32 29 27 22 19 2 51 42 40 33 31 26 20 22 3 60 46 38 32 28 22 22 19 4 56 60 41 36 29 25 22 18 5 47 39 33 25 26 28 21 18 6 42 38 37 33 30 27 25 20 7 51 43 40 30 28 25 27 19 8 60 60 40 32 26 29 25 17 Figure 3A: Effects of ACPA 0.001 µg/rat + Lithium on escape latency (Time): ACPA 0.001 µg/rat + Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 52 46 33 24 19 13 7 9 2 60 60 40 25 20 16 8 7 3 60 44 38 21 20 14 6 8 4 60 49 37 27 22 14 10 7 5 48 41 31 17 19 16 11 8 6 60 44 32 19 13 11 7 11 7 42 53 37 22 17 14 10 9 8 49 35 29 18 14 11 6 10 Figure 3A: Effects of ACPA 0.001 µg/rat + Lithium on escape latency (Time): ACPA 0.001 µg/rat + Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 48 33 21 19 15 10 6 2 60 42 27 25 17 14 9 7 3 48 53 29 21 18 16 9 6 4 41 32 36 22 23 22 13 6 5 60 48 31 18 16 16 10 9 6 55 41 35 19 17 14 7 10 7 50 60 41 27 22 19 13 11 8 60 60 47 33 21 12 8 7 Figure 3A: Effects of ACPA 0.001 µg/rat + Lithium on escape latency (Time): ACPA 0.001 µg/rat + Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 41 35 21 20 15 10 11 2 60 46 32 22 17 18 11 8 3 46 36 35 31 22 20 15 11 4 41 51 31 24 16 18 11 10 5 44 52 39 32 23 16 9 9 6 60 41 27 21 16 18 8 7 7 58 45 30 24 17 16 9 6 8 51 44 37 26 14 13 10 7 Figure 3A: Effects of ACPA 0.001 µg/rat + Lithium on escape latency (Time): ACPA 0.001 µg/rat + Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S13 Figure 3A: Effects of AM251 1 ng/rat + Lithium on escape latency (Time) Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 49 53 39 33 30 26 18 17 2 60 52 38 35 26 22 21 20 3 52 51 42 31 24 29 22 21 4 52 37 32 25 26 28 24 18 5 60 42 35 32 32 24 19 17 6 53 44 39 31 29 22 24 18 7 60 41 40 27 29 29 20 15 8 52 45 41 36 32 24 25 19 Figure 3A: Effects of AM251 1 ng/rat + Lithium on escape latency (Time): AM251 1 ng/rat + Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 60 51 33 20 16 12 8 6 2 60 36 35 21 15 10 9 11 3 43 34 26 21 12 11 8 10 4 54 53 33 22 19 16 11 7 5 45 56 41 27 22 16 12 9 6 55 45 28 23 15 14 9 6 7 60 44 28 33 20 12 12 6 8 58 60 48 32 26 14 11 7 Figure 3A: Effects of AM251 1 ng/rat + Lithium on escape latency (Time): AM251 1 ng/rat + Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 52 43 33 19 24 20 12 8 2 52 60 41 22 17 14 10 7 3 60 46 31 17 15 15 9 8 4 58 43 32 22 24 20 16 11 5 60 55 40 32 26 18 10 7 6 48 36 31 26 21 15 7 8 7 51 41 27 21 22 17 9 6 8 42 44 29 24 18 14 11 6 Figure 3A: Effects of AM251 1 ng/rat + Lithium on escape latency (Time): AM251 1 ng/rat + Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 53 36 34 19 17 11 10 7 2 50 32 38 26 17 19 12 11 3 60 42 29 22 21 17 11 9 4 60 51 35 34 22 19 14 11 5 60 39 29 21 17 12 8 8 6 60 60 47 27 19 13 9 8 7 46 44 33 28 21 19 15 7 8 49 41 37 22 15 14 10 7 Figure 3A: Effects of AM251 1 ng/rat + Lithium on escape latency (Time): AM251 1 ng/rat + Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S14 Figure 3B: Effects of Lithium on traveled distance Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1467 1210 891 756 535 387 232 222 2 1398 1110 943 589 422 349 250 241 3 1366 1154 852 652 431 316 212 209 4 1424 1245 989 737 666 366 287 291 5 1767 1412 1042 792 623 404 230 287 6 1571 1291 958 670 452 296 302 245 7 1788 1491 1123 842 587 376 240 223 8 1612 1287 876 755 617 345 292 310 Figure 3B: Effects of Lithium on traveled distance: Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1745 1444 854 764 575 316 363 187 2 1811 1761 1177 909 500 333 225 266 3 1431 1346 791 877 456 437 278 201 4 1277 829 930 741 494 647 337 324 5 1662 1134 929 578 679 309 341 178 6 1591 1226 711 502 477 295 552 284 7 1770 956 889 820 635 341 372 335 8 1345 1145 632 804 338 511 221 269 Figure 3B: Effects of Lithium on traveled distance: Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1763 1567 965 908 711 335 210 290 2 1633 1803 871 701 789 481 244 351 3 1361 1141 912 633 771 246 279 189 4 1789 1217 1160 669 504 472 345 146 5 1736 1557 893 454 349 543 379 190 6 1661 1168 1287 913 781 329 288 331 7 1237 1290 978 777 650 266 482 281 8 1311 1701 1200 581 736 491 351 310 Figure 3B: Effects of Lithium on traveled distance: Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1631 1770 1257 733 770 478 282 215 2 1242 1188 878 967 478 490 167 200 3 1745 1201 1224 890 512 456 198 244 4 1771 1575 1040 689 455 665 389 225 5 1756 1320 1202 811 709 343 355 359 6 1180 906 1021 631 679 356 303 335 7 1642 1210 1143 666 502 255 319 241 8 1244 922 952 783 771 518 341 258 Figure 3B: Effects of Lithium on traveled distance: Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S15 Figure 3B: Effects of ACPA 0.001 µg/rat + Lithium on traveled distance Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1744 1622 1346 1067 930 875 729 666 2 1591 1326 1261 1081 1008 845 701 724 3 1771 1404 1167 1051 879 699 731 678 4 1690 1786 1255 1131 919 804 702 621 5 1414 1225 1089 825 845 896 691 634 6 1311 1187 1125 1090 955 866 798 689 7 1579 1341 1255 977 888 810 845 633 8 1759 1764 1241 1025 843 900 808 591 Figure 3B: Effects of ACPA 0.001 µg/rat + Lithium on traveled distance: ACPA 0.001 µg/rat + Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1626 1387 1098 809 662 411 234 321 2 1761 1755 1265 838 688 536 252 251 3 1746 1369 1214 743 701 435 211 230 4 1789 1479 1189 898 738 447 351 250 5 1465 1266 1031 572 641 523 367 287 6 1791 1357 1059 650 398 332 245 352 7 1302 1644 1233 749 577 437 310 279 8 1486 1124 967 623 445 346 219 312 Figure 3B: Effects of ACPA 0.001 µg/rat + Lithium on traveled distance: ACPA 0.001 µg/rat + Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1761 1439 1087 751 651 487 325 204 2 1754 1313 889 830 562 455 301 232 3 1445 1667 952 711 613 521 293 211 4 1278 1044 1200 742 787 760 402 209 5 1792 1456 1078 622 558 541 323 267 6 1698 1288 1136 654 583 444 242 299 7 1579 1810 1277 903 756 645 409 332 8 1777 1754 1438 1102 721 379 223 240 Figure 3B: Effects of ACPA 0.001 µg/rat + Lithium on traveled distance: ACPA 0.001 µg/rat + Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1812 1283 1134 742 702 474 312 367 2 1782 1203 1065 783 555 563 355 227 3 1389 1189 1144 1034 771 728 476 353 4 1287 1610 1021 810 509 572 367 312 5 1343 1639 1248 1098 798 514 256 278 6 1767 1276 912 759 493 568 235 234 7 1722 1420 1051 794 526 511 270 204 8 1589 1388 1202 887 438 421 326 224 Figure 3B: Effects of ACPA 0.001 µg/rat + Lithium on traveled distance: ACPA 0.001 µg/rat + Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S16 Figure 3B: Effects of AM251 1 ng/rat + Lithium on traveled distance Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1433 1645 1214 1091 969 850 590 584 2 1741 1605 1184 1144 861 712 694 670 3 1600 1567 1311 978 790 933 731 702 4 1589 1154 1084 821 856 893 761 603 5 1756 1290 1092 1010 1041 778 648 562 6 1626 1354 1178 966 926 742 795 584 7 1760 1245 1234 900 911 949 681 438 8 1617 1337 1228 1187 1014 782 784 610 Figure 3B: Effects of AM251 1 ng/rat + Lithium on traveled distance: AM251 1 ng/rat + Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1756 1572 1071 702 501 371 267 212 2 1788 1128 1120 733 446 321 300 345 3 1333 1079 870 731 371 345 281 313 4 1658 1622 1064 759 677 481 376 238 5 1399 1690 1276 879 760 469 391 298 6 1672 1402 901 788 443 406 295 234 7 1746 1378 912 1076 712 391 385 211 8 1721 1792 1448 1025 864 421 345 262 Figure 3B: Effects of AM251 1 ng/rat + Lithium on traveled distance: AM251 1 ng/rat + Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1602 1315 1035 648 797 701 398 298 2 1621 1798 1289 751 589 421 321 253 3 1763 1398 998 576 457 445 301 279 4 1712 1321 1012 754 802 689 523 365 5 1801 1677 1281 1008 889 594 309 245 6 1443 1119 1002 865 723 453 234 287 7 1578 1287 893 730 744 602 289 225 8 1300 1366 915 776 610 418 345 221 Figure 3B: Effects of AM251 1 ng/rat + Lithium on traveled distance: AM251 1 ng/rat + Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 1645 1156 1087 651 571 332 309 248 2 1564 1076 1203 869 598 661 387 368 3 1777 1298 929 739 711 567 353 296 4 1792 1603 1099 1072 748 656 410 354 5 1812 1212 903 742 564 377 278 288 6 1756 1803 1798 909 639 422 281 276 7 1400 1378 1071 920 728 667 462 239 8 1478 1267 1188 746 433 409 311 241 Figure 3B: Effects of AM251 1 ng/rat + Lithium on traveled distance: AM251 1 ng/rat + Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S17 Figure 3C: Effects of Lithium on swimming speed Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.93 31.02 33.00 34.36 33.43 32.25 33.14 37.00 2 30.39 31.71 32.51 34.64 30.14 31.72 35.71 34.42 3 31.04 32.05 32.76 34.31 30.78 31.60 35.33 34.83 4 30.29 31.12 32.96 35.09 35.05 30.50 35.87 36.37 5 29.45 30.04 33.61 33.00 34.61 28.85 32.85 31.88 6 31.42 30.73 33.03 35.26 30.13 29.60 33.55 35.00 7 29.80 30.42 34.03 33.68 34.52 31.33 34.28 37.16 8 31.00 31.39 32.44 34.31 34.27 31.36 36.50 34.44 Figure 3C: Effects of Lithium on swimming speed: Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.08 30.08 32.84 34.72 33.82 31.60 30.25 31.16 2 30.18 29.35 31.81 32.46 33.33 30.27 32.14 33.25 3 30.44 29.91 32.95 32.48 32.57 31.21 34.75 33.50 4 30.40 33.16 33.21 33.68 32.93 34.05 33.70 32.40 5 30.21 33.35 32.03 32.11 33.95 34.33 34.10 29.66 6 31.19 30.65 33.85 33.46 34.07 32.77 32.47 31.55 7 29.50 30.83 32.92 32.80 33.42 31.00 31.00 33.50 8 30.56 34.69 33.26 33.50 30.72 34.06 31.57 33.62 Figure 3C: Effects of Lithium on swimming speed: Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.38 30.72 31.12 33.62 33.85 30.45 35.00 32.22 2 30.81 30.05 32.25 33.38 34.30 34.35 34.85 31.90 3 30.24 33.55 31.44 33.31 33.52 30.75 34.87 31.50 4 29.81 31.20 35.15 33.45 33.60 33.71 28.75 29.20 5 28.93 31.14 33.07 32.42 31.72 33.93 29.15 31.66 6 29.66 31.56 30.64 32.60 35.50 29.90 32.00 30.09 7 30.17 29.31 31.54 35.31 34.21 29.55 34.42 31.22 8 30.48 29.84 34.28 34.17 35.04 35.07 29.25 31.00 Figure 3C: Effects of Lithium on swimming speed: Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.65 29.50 30.65 33.31 33.47 34.14 31.33 30.71 2 29.57 33.94 33.76 31.19 26.55 32.66 27.83 33.33 3 29.08 33.36 30.60 31.78 26.94 32.57 28.28 30.50 4 29.51 30.88 31.51 32.80 30.33 33.25 29.92 32.14 5 29.26 30.00 30.82 32.44 32.22 31.18 27.30 32.63 6 30.25 32.35 30.93 35.05 32.33 29.66 30.30 33.50 7 29.85 29.51 31.75 35.05 33.46 31.87 29.00 30.12 8 29.61 31.79 31.73 32.62 32.12 34.53 31.00 32.25 Figure 3C: Effects of Lithium on swimming speed: Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S18 Figure 3C: Effects of ACPA 0.001 µg/rat + Lithium on swimming speed Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.06 30.60 30.59 33.34 32.06 32.40 33.13 35.05 2 31.19 31.57 31.52 32.75 32.51 32.50 35.05 32.90 3 29.51 30.52 30.71 32.84 31.39 31.77 33.22 35.68 4 30.17 29.76 30.60 31.41 31.68 32.16 31.90 34.50 5 30.08 31.41 33.00 33.00 32.50 32.00 32.90 35.22 6 31.21 31.22 30.40 33.03 31.83 32.07 31.92 34.45 7 30.96 31.18 31.37 32.56 31.71 32.40 31.29 33.31 8 29.31 29.40 31.02 32.03 32.42 31.03 32.32 34.76 Figure 3C: Effects of ACPA 0.001 µg/rat + Lithium on swimming speed: ACPA 0.001 µg/rat + Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 31.26 30.15 33.27 33.70 34.84 31.61 33.42 35.66 2 29.35 29.25 31.62 33.52 34.40 33.50 31.50 35.85 3 29.10 31.11 31.94 35.38 35.05 31.07 35.16 28.75 4 29.81 30.18 32.13 33.25 33.54 31.92 35.10 35.71 5 30.52 30.87 33.25 33.64 33.73 32.68 33.36 35.87 6 29.85 30.84 33.09 34.21 30.61 30.18 35.00 32.00 7 31.00 31.01 33.32 34.04 33.94 31.21 31.00 31.00 8 30.32 32.11 33.34 34.61 31.78 31.45 36.50 31.20 Figure 3C: Effects of ACPA 0.001 µg/rat + Lithium on swimming speed: ACPA 0.001 µg/rat + Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.35 29.97 32.93 35.76 34.26 32.46 32.50 34.00 2 29.23 31.26 32.92 33.20 33.05 32.50 33.44 33.14 3 30.10 31.45 32.82 33.85 34.05 32.56 32.55 35.16 4 31.17 32.62 33.33 33.72 34.21 34.54 30.92 34.83 5 29.86 30.33 34.77 34.55 34.87 33.81 32.30 29.66 6 30.87 31.41 32.45 34.42 34.29 31.71 34.57 29.90 7 31.58 30.16 31.14 33.44 34.36 33.94 31.46 30.18 8 29.61 29.23 30.59 33.39 34.33 31.58 27.87 34.28 Figure 3C: Effects of ACPA 0.001 µg/rat + Lithium on swimming speed: ACPA 0.001 µg/rat + Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 30.20 31.29 32.40 35.33 35.10 31.60 31.20 33.36 2 29.70 26.15 33.28 35.59 32.64 31.27 32.27 28.37 3 30.19 33.02 32.68 33.35 35.04 36.40 31.73 32.09 4 31.39 31.56 32.93 33.75 31.81 31.77 33.36 31.20 5 30.52 31.51 32.00 34.31 34.69 32.12 28.44 30.88 6 29.45 31.12 33.77 36.14 30.81 31.55 29.37 33.42 7 29.68 31.55 35.03 33.08 30.94 31.93 30.00 34.00 8 31.15 31.54 32.48 34.11 31.28 32.38 32.60 32.00 Figure 3C: Effects of ACPA 0.001 µg/rat + Lithium on swimming speed: ACPA 0.001 µg/rat + Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S19 Figure 3C: Effects of AM251 1 ng/rat + Lithium on swimming speed Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.24 31.03 31.12 33.06 32.30 32.69 32.77 34.35 2 29.01 30.86 31.15 32.68 33.11 32.36 33.04 33.50 3 30.76 30.72 31.21 31.54 32.91 32.17 33.22 33.42 4 30.55 31.18 33.87 32.84 32.92 31.89 31.70 33.50 5 29.26 30.71 31.20 31.56 32.53 32.41 34.10 33.05 6 30.67 30.77 30.20 31.16 31.93 33.72 33.12 32.44 7 29.33 30.36 30.85 33.33 31.41 32.72 34.05 29.20 8 31.09 29.71 29.95 32.97 31.68 32.58 31.36 32.10 Figure 3C: Effects of AM251 1 ng/rat + Lithium on swimming speed: AM251 1 ng/rat + Saline Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 29.26 30.82 32.45 35.10 31.31 30.91 33.37 35.33 2 29.80 31.33 31.11 34.90 29.73 32.10 33.33 31.36 3 31.00 31.73 33.46 34.80 30.91 31.36 35.12 31.30 4 30.70 30.60 32.24 34.50 35.63 30.06 34.18 34.00 5 31.08 30.17 31.12 32.55 34.54 29.31 32.58 33.11 6 30.40 31.15 32.17 34.26 29.53 29.00 32.77 39.00 7 29.10 31.31 32.57 32.60 35.60 32.58 32.08 35.16 8 29.67 29.86 30.16 32.03 33.23 30.07 31.36 37.42 Figure 3C: Effects of AM251 1 ng/rat + Lithium on swimming speed: AM251 1 ng/rat + Lithium 0.5 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 30.80 30.58 31.36 34.10 33.20 35.05 33.16 37.25 2 31.17 29.96 31.43 34.13 34.64 30.07 32.10 36.14 3 29.38 30.39 32.19 33.88 30.46 29.66 33.44 34.87 4 29.51 30.72 31.62 34.27 33.41 34.45 32.68 33.18 5 30.10 30.49 32.02 31.50 34.19 33.00 30.90 35.00 6 30.06 31.08 32.22 33.26 34.42 30.20 33.42 35.87 7 30.94 31.39 33.07 34.76 33.81 35.41 32.11 37.50 8 30.95 31.04 31.55 32.33 33.88 29.85 31.36 36.83 Figure 3C: Effects of AM251 1 ng/rat + Lithium on swimming speed: AM251 1 ng/rat + Lithium 1 mg/kg Rat Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7 Trial 8 1 31.03 32.11 31.97 34.26 33.58 30.18 30.90 35.42 2 31.28 33.62 31.65 33.42 35.17 34.78 32.25 33.45 3 29.61 30.90 32.03 33.59 33.85 33.35 32.09 32.88 4 29.86 31.43 31.40 31.52 34.00 34.52 29.28 32.18 5 30.20 31.07 31.13 35.33 33.17 31.41 34.75 36.00 6 29.26 30.05 38.25 33.66 33.63 32.46 31.22 34.50 7 30.43 31.31 32.45 33.85 34.66 35.10 30.80 34.14 8 30.16 30.90 32.10 33.90 28.86 29.21 31.10 34.42 Figure 3C: Effects of AM251 1 ng/rat + Lithium on swimming speed: AM251 1 ng/rat + Lithium 5 mg/kg EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S20 Raw Data Escape latency (Time): sec Traveled distance: cm Swimming speed: cm/sec Probes Supplementary Tables “4” for Figure 4: Effects of different doses of all drugs (ACPA, AM251 and lithium) on spatial memory retrieval were shown. Twenty-four hours after training, all animals (eight rats in each group), were trained for the probe test in MWM apparatus. EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S21 Figure 4A: Effects of all drugs on escape latency (Time) Rat Saline ACPA 0.001 µg/rat ACPA 0.01 µg/rat ACPA 1 µg/rat 1 26 16 16 13 2 24 29 9 14 3 31 24 18 6 4 18 20 14 10 5 19 19 12 14 6 28 20 15 15 7 19 20 14 12 8 20 21 15 10 Figure 4A: Effects of ACPA on escape latency (Time) Rat Saline AM251 1 ng/rat AM251 10 ng/rat AM251 100 ng/rat 1 26 19 19 23 2 24 22 21 25 3 31 20 21 23 4 18 30 20 22 5 19 21 24 24 6 28 22 22 19 7 19 20 24 22 8 20 18 22 19 Figure 4A: Effects of AM251 on escape latency (Time) Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 26 20 19 16 2 24 24 20 14 3 31 22 27 15 4 18 23 24 15 5 19 18 25 12 6 28 28 21 13 7 19 27 26 14 8 20 19 22 12 Figure 4A: Effects of Lithium on escape latency (Time) EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S22 Figure 4B: Effects of all drugs on traveled distance Rat Saline ACPA 0.001 µg/rat ACPA 0.01 µg/rat ACPA 1 µg/rat 1 892 636 622 414 2 851 991 385 459 3 1020 868 747 222 4 723 809 574 402 5 783 768 430 536 6 952 798 577 582 7 775 814 562 436 8 792 829 587 387 Figure 4B: Effects of ACPA on traveled distance Rat Saline AM251 1 ng/rat AM251 10 ng/rat AM251 100 ng/rat 1 892 782 798 873 2 851 851 810 892 3 1020 823 827 855 4 723 1009 809 836 5 783 812 842 878 6 952 852 859 810 7 775 820 867 848 8 792 798 852 795 Figure 4B: Effects of AM251 on traveled distance Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 892 814 782 623 2 851 864 800 528 3 1020 820 975 582 4 723 842 892 592 5 783 784 912 428 6 952 982 823 432 7 775 962 972 487 8 792 794 824 440 Figure 4B: Effects of Lithium on traveled distance EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S23 Raw Data Escape latency (Time): sec Traveled distance: cm Swimming speed: cm/sec Probes Supplementary Tables “5” for Figure 5: Effects of interaction between cannabinoid drugs and lithium on spatial memory re- trieval were shown. Twenty-four hours after training, all animals (eight rats in each group), were trained for the probe test in MWM apparatus. EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S24 Figure 5A: Effects of interaction between cannabinoid drugs and lithium on escape latency (Time) Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 26 20 19 16 2 24 24 20 14 3 31 22 27 15 4 18 23 24 15 5 19 18 25 12 6 28 28 21 13 7 19 27 26 14 8 20 19 22 12 Figure 5A: Effects of Lithium on escape latency (Time) Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 16 12 14 16 2 29 14 12 19 3 24 12 15 22 4 20 14 16 15 5 19 16 11 21 6 20 13 13 21 7 20 15 15 19 8 21 12 12 18 Figure 5A: Effects of ACPA 0.001 µg/rat + Lithium on escape latency (Time) Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 19 14 6 19 2 22 16 11 28 3 20 9 12 20 4 30 13 12 29 5 21 12 16 17 6 22 17 12 27 7 20 8 12 21 8 18 11 11 25 Figure 5A: Effects of AM251 1 ng/rat + Lithium on escape latency (Time) EXCLI Journal 2018;17:916-934 – ISSN 1611-2156 Received: July 07, 2018, accepted: August 27, 2018, published: September 20, 2018 S25 Figure 5B: Effects of interaction between cannabinoid drugs and lithium on traveled distance Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 892 814 782 623 2 851 864 800 528 3 1020 820 975 582 4 723 842 892 592 5 783 784 912 428 6 952 982 823 432 7 775 962 972 487 8 792 794 824 440 Figure 5B: Effects of Lithium on traveled distance Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 636 416 543 602 2 991 571 408 789 3 868 421 618 842 4 809 584 645 578 5 768 625 402 802 6 798 472 489 834 7 814 575 607 793 8 829 438 434 783 Figure 5B: Effects of ACPA 0.001 µg/rat + Lithium on traveled distance Rat Saline Lithium 0.5 mg/kg Lithium 1 mg/kg Lithium 5 mg/kg 1 782 514 269 799 2 851 598 396 987 3 823 389 419 841 4 1009 461 405 962 5 812 424 628 757 6 852 752 443 921 7 820 361 425 816 8 798 404 421 902 Figure 5B: Effects of AM251 1 ng/rat + Lithium on traveled distance