Table 1.
Summary of repeated dosing of (R,S)-ketamine in the rodent forced swim test (FST).
| Publication | Species | Strain | Sex | Age at start | Dose (mg/kg) | # of repeats | Time delay | Stressor | Immobility |
|---|---|---|---|---|---|---|---|---|---|
| Thelen et al. (39) | Mice | C57 | M | 8–12 wk | 3 | Once daily for 21 days | 24 h | Unstr | No Ch |
| C57 | M | 8–12 wk | 5 | Once daily for 21 days | 24 h | Unstr | No Ch | ||
| C57 | M | 8–12 wk | 10 | Once daily for 21 days | 24 h | Unstr | Decr | ||
| C57 | F | 8–12 wk | 3 | Once daily for 21 days | 24 h | Unstr | No Ch | ||
| C57 | F | 8–12 wk | 5 | Once daily for 21 days | 24 h | Unstr | No Ch | ||
| C57 | F | 8–12 wk | 10 | Once daily for 21 days | 24 h | Unstr | Incr | ||
| Clarke et al. (40) | Mice | CD-1 | M | 8–10 wk | 10 | Single injection | 1 h | Unstr | Decr |
| CD-1 | M | 8–10 wk | 10 | Single injection | 2, 5, or 8 days | Unstr | No Ch | ||
| CD-1 | M | 8–10 wk | 10 | 3 repeats over 2 weeks | 2 days | Unstr | Decr | ||
| CD-1 | M | 8–10 wk | 10 | 3 repeats over 2 weeks | 8 days | Unstr | Decr | ||
| Krimmel et al. (41) | Mice | CD-1 | M | 7 wk | 10 | Single injection | 1 h | Unstr | Decr |
| CD-1 | M | 7 wk | 10 | Single injection | 24 h | Unstr | Decr | ||
| CD-1 | F | 7 wk | 10 | Single injection | 1 h | Unstr | Decr | ||
| CD-1 | F | 7 wk | 10 | Single injection | 24 h | Unstr | No Ch | ||
| CD-1 | M | 7 wk | 10 | Every 2nd week for 4 weeks | 1 h | Unstr | Decr | ||
| CD-1 | M | 7 wk | 10 | Every 2nd week for 4 weeks | 24 h | Unstr | Decr | ||
| CD-1 | F | 7 wk | 10 | Every 2nd week for 4 weeks | 1 h | Unstr | Decr | ||
| CD-1 | F | 7 wk | 10 | Every 2nd week for 4 weeks | 24 h | Unstr | No Ch | ||
| CD-1 | M | 7 wk | 10 | Every 2nd week for 3 weeks | 1 h | Unstr | Decr | ||
| CD-1 | M | 7 wk | 10 | Every 2nd week for 3 weeks | 24 h | Unstr | Decr | ||
| CD-1 | F | 7 wk | 10 | Every 2nd week for 3 weeks | 1 h | Unstr | No Ch | ||
| CD-1 | F | 7 wk | 10 | Every 2nd week for 3 weeks | 24 h | Unstr | No Ch | ||
| Neves et al. (42) | Mice | CF-1 | M | Adult | 30 (S-ket) | Single injection | 24 h | Unstr | No Ch |
| CF-1 | M | Adult | 30 (S-ket) | Once daily for 14 days | 2 days | Unstr | Decr | ||
| CF-1 | M | Adult | 30 (S-ket) | Once daily for 14 days | 4 days | Unstr | No Ch | ||
| CF-1 | M | Adult | 30 (S-ket) | Once daily for 14 days | 8 days | Unstr | No Ch | ||
| CF-1 | M | Adult | 30 (S-ket) | Once daily for 14 days | 15 days | Unstr | No Ch | ||
| CF-1 | M | Adult | 30 (S-ket) | Once daily for 14 days | 22 days | Unstr | No Ch | ||
| CF-1 | M | Adult | 30 (S-ket) | Once daily for 5 days | 24 h | Unstr | No Ch | ||
| Kara et al. (43) | Mice | ICR | Mix | 10–12 wk | 5 | Single injection | 30 min | Unstr | No Ch |
| ICR | Mix | 10–12 wk | 10 | Single injection | 30 min | Unstr | Decr | ||
| ICR | Mix | 10–12 wk | 5 | Once daily for 3 weeks | 30 min | Unstr | No Ch | ||
| ICR | Mix | 10–12 wk | 10 | Once daily for 3 weeks | 30 min | Unstr | No Ch | ||
| Suárez-Santiago et al. (38) | Mice | NIH | M | 2 months | 10 | Once daily for 5 days | 20 min | Unstr | Incr |
| Chatterjee et al. (44) | Mice | Swiss | M | Not stated | 100 | Single injection | 24 h | Unstr | No Ch |
| Swiss | M | Not stated | 100 | Once daily for 10 days | 30 min | Unstr | Incr | ||
| Swiss | M | Not stated | 100 | Once daily for 10 days | 5 days | Unstr | Incr | ||
| Swiss | M | Not stated | 100 | Once daily for 10 days | 10 days | Unstr | Incr | ||
| Popik et al. (45) | Mice | Swiss | M | Not stated | 1.25 | Single injection | 30 min, 2 weeks | Unstr | No Ch |
| Swiss | M | Not stated | 2.5 | Single injection | 30 min, 2 weeks | Unstr | No Ch | ||
| Swiss | M | Not stated | 5 | Single injection | 30 min, 2 weeks | Unstr | No Ch | ||
| Swiss | M | Not stated | 10 | Single injection | 30 min, 2 weeks | Unstr | No Ch | ||
| Swiss | M | Not stated | 50 | Single injection | 30 min, 2 weeks | Unstr | Decr | ||
| Singh et al. (46) | Mice | Swiss | M | Adult | 100 | Once daily for 10 days | 24 h | Unstr | Incr |
| Hou et al. (47) | Mice | Sw-K | M | Not stated | 25 | Single injection | 24 h | Unstr | No Ch |
| Sw-K | M | Not stated | 50 | Single injection | 24 h | Unstr | No Ch | ||
| Sw-K | M | Not Stated | 100 | Single injection | 24 h | Unstr | No Ch | ||
| Sw-K | M | Not stated | 25 | Once daily for 7 days | 24 h | Unstr | No Ch | ||
| Sw-K | M | Not stated | 50 | Once daily for 7 days | 24 h | Unstr | No Ch | ||
| Sw-K | M | Not stated | 100 | Once daily for 7 days | 24 h | Unstr | Incr | ||
| Owolabi et al. (48) | Mice | Albino | Mix | Adult | 3 | Single injection | 5 min | Unstr | Decr |
| Albino | Mix | Adult | 15 | Single injection | 5 min | Unstr | Decr | ||
| Albino | Mix | Adult | 15 | Once daily for 21 days | 24 h | Unstr | Incr | ||
| Zhang et al. (49) | Rat | S-D | M | 7 wk | 10 | Once daily for 3 days | 15–17 h | UCMS | Decr |
| S-D | M | 7 wk | 10 | Once daily for 7 days | 15–17 h | UCMS | Decr | ||
| S-D | M | 7 wk | 10 | Once every 3 days for 21 days | 15–17 h | UCMS | Decr | ||
| S-D | M | 7 wk | 10 | Once every 7 days for 21 days | 15–17 h | UCMS | Decr | ||
| Jiang et al. (50) | Rat | S-D | M | 35–49 days | 10 | Once daily for 14 days | 1 week | CUS | No Ch |
| S-D | M | 35–49 days | 10 | Once daily for 14 days | 7 weeks | CUS | Decr | ||
| Li et al. (51) | Rat | S-D | M | 28 days old | 20 | Once daily for 21 days | 24 h | Unstr | No Ch |
| S-D | M | 28 days old | 30 | Once daily for 21 days | 24 h | Unstr | No Ch | ||
| Parise et al. (36) | Rat | S-D | M | 35–49 days | 20 | Single injection | 1 h | CUS | Decr |
| S-D | M | 75–89 days | 20 | Twice daily for 15 days | 2 months | CUS | Decr | ||
| S-D | M | 35–49 days | 20 | Twice daily for 15 days | 2 months | CUS | Decr | ||
| S-D | M | 35–49 days | 5 | Twice in a day | 24 h | Unstr | No Ch | ||
| S-D | M | 35–49 days | 10 | Twice in a day | 24 h | Unstr | Decr | ||
| S-D | M | 35–49 days | 20 | Twice in a day | 24 h | Unstr | Decr | ||
| Getachew and Tizabi (52) | Rat | Wist | M | 8–10 wk | 2.5 + alc | Once daily for 7 days | 18 h | Unstr | Decr |
| Garcia et al. (53) | Rat | Wist | M | 60 days | 5 | Once daily for 14 days | 1 h | Unstr | Decr |
| Wist | M | 60 days | 10 | Once daily for 14 days | 1 h | Unstr | Decr | ||
| Wist | M | 60 days | 15 | Once daily for 14 days | 1 h | Unstr | Decr | ||
| Chindo et al. (54) | Rat | Wist | Mix | Adult | 30 | Single injection | 24 h | Unstr | No Ch |
| Wist | Mix | Adult | 1 | Once daily for 10 days | 24 h, then weekly | Unstr | No Ch | ||
| Wist | Mix | Adult | 10 | Once daily for 10 days | 24 h, then weekly | Unstr | No Ch | ||
| Wist | Mix | Adult | 30 | Once daily for 10 days | 24 h, then weekly | Unstr | Incr | ||
| Wist | Mix | Adult | 50 | Once daily for 10 days | 24 h, then weekly | Unstr | Incr | ||
| De Cartágenes et al. (55) | Rat | Wist | F | 35 days | 10 | Once daily for 3 days | 3 h | Unstr | Incr |
| Réus et al. (56) | Rat | Wist | M | 3 months | 30 | Once daily for 14 days | 1 h | Unstr | Decr |
| Ecevitoglu et al. (57) | Rat | Wist | M | Adult | Up to 0.2/day | 16 days in drinking water | 24 h then 48 h | Unstr | No Ch |
| Wist | M | Adult | Up to 0.4/day | 16 days in drinking water | 24 h then 48 h | Unstr | Decr | ||
| Popik et al. (45) | Rat | Wist | M | Not Stated | 160 | Single injection | 6 days, 7 days | Unstr | No Ch |
| Wist | M | Not Stated | 50 | Once daily for 2 days | 40 min | Unstr | Decr | ||
| Wist | M | Not Stated | 50 | Twice daily for 2 weeks | 40 min | Unstr | Decr | ||
| Aricioglu et al. (58) | Rat | Wist | M | 8–10 wk | 10 | Single injection | 12 h | UCMS | No Ch |
| Wist | M | 8–10 wk | 10 | Once daily for 3 weeks | 12 h | UCMS | Decr | ||
| Tizabi et al. (59) | Rat | Wist | F | Adult | 0.5 | Single injection | 30 min | Unstr | No Ch |
| Wist | F | Adult | 2.5 | Single injection | 30 min | Unstr | No Ch | ||
| Wist | F | Adult | 5 | Single injection | 30 min | Unstr | No Ch | ||
| WKY | F | Adult | 0.5 | Single injection | 30 min | Unstr | No Ch | ||
| WKY | F | Adult | 2.5 | Single injection | 30 min | Unstr | Decr | ||
| WKY | F | Adult | 5 | Single injection | 30 min | Unstr | Decr | ||
| Wist | F | Adult | 0.5 | Once daily for 10 days | 20–22 h | Unstr | No Ch | ||
| Wist | F | Adult | 2.5 | Once daily for 10 days | 20–22 h | Unstr | No Ch | ||
| Wist | F | Adult | 5 | Once daily for 10 days | 20–22 h | Unstr | No Ch | ||
| WKY | F | Adult | 0.5 | Once daily for 10 days | 20–22 h | Unstr | No Ch | ||
| WKY | F | Adult | 2.5 | Once daily for 10 days | 20–22 h | Unstr | Decr | ||
| WKY | F | Adult | 5 | Once daily for 10 days | 20–22 h | Unstr | Decr | ||
| WKY | F | Adult | 2.5 | Once daily for 10 days | 1 week | Unstr | Decr | ||
| WKY | F | Adult | 2.5 | Once daily for 10 days | 2 weeks | Unstr | No Ch | ||
| Akinfiresoye and Tizabi (60) | Rat | WKY | M | Adult | 0.25 | Once daily for 11 days | 20 min | Unstr | No Ch |
| WKY | M | Adult | 0.5 | Once daily for 11 days | 20 min | Unstr | Decr |
This table comprises the 24 mice and rat studies from our literature search that used repeated administration of ketamine in the FST. The “Immobility” column in table indicates whether ketamine decreased or increased this measure relative to vehicle-injected animals subjected to the same stress condition (i.e., stressed or unstressed), in a statistically significant manner where p < 0.05. The “Time Delay” column represents the amount of time between the last (or only) administration of ketamine and when the FST was carried out. All experiments that used a single injection are marked in yellow, and those that used chronic stress are marked in red. Experiments that showed a statistically significant decrease in immobility are marked in green, whereas those with a significant increase are marked in blue. C57, C57BL/6J; Sw-K, Swiss-Kunming; S-D, Sprague-Dawley; Wist, Wistar; M, male; F, female; Mix, males and females; wk, weeks; S-ket, (S)-ketamine; alc, alcohol; Unstr, unstressed; Decr, decreased; Incr, increased; No Ch, no change; UCMS, unpredictable chronic mild stress; CUS, chronic unpredictable stress.