Table 1.
Acute effects of ketamine.
| References | Species and strain | Ketamine—supplier and dose | Behavioral alterations | Molecular alterations |
|---|---|---|---|---|
| ACUTE EFFECTS OF KETAMINE | ||||
| Burgdorf et al., 2013 | Male adult (2–3 months) Sprague-Dawley rats | Fort Dodge (Butler, USA), I.V., I.P., and S.C. 10 mg/kg | Reduced immobility in FST 20–60 min and 24 h post i.p. Injection (10 mg/kg). Reduced latency to feed in the NIH 1 h post 10 mg/kg i.v. | Increased NR2B and GluR1 expression in the mPFC and HC 24 h post-injection |
| Carrier and Kabbaj, 2013 | Male (250–270 g) and female (200–225 g) Sprague-Dawley rats | Fort Dodge (Butler Schein), Inc. 2.5–0 mg/kg | Latency to feed was reduced in the NSF 24 h post-injection (5 and 10 mg/kg). Increased sucrose consumption of males 48 h post-injection in the SPT. Reduced immobility in FST in males & females 30 min post-injection | Increased mTOR phosphorylation in males and females, reduced eEF2 phosphorylation in males (5 mg/kg) |
| Gigliucci et al., 2013 | Male (280–320 g) Sprague- Dawley rats | Vetoquinol Ltd., UK (1.0 mg/ml). 10–25 mg/kg i.p. | Rats exhibited antidepressant-like effects in the FST at 1 or 24 h after a single injection of ketamine. Ketamine was ineffective following 3 injections (24, 5 and 1 h prior to testing). Ketamine (25 mg/kg) reversed stress-induced immobility; this was prevented by pCPA treatment at 24 h but not at 1 h post-injection | Depletion of cortical serotonin levels by pCPA (1.0 mg/kg once daily for 3 days) attenuated the antidepressant-like effect of ketamine in the FST |
| Koike et al., 2013a | Male Sprague-Dawley rats (185–325 g at testing) | Ketalar® Sankyo Yell Pharmaceutical Co., Ltd., 1–10 mg/kg i.p. | Ketamine (10 mg/kg) decreased immobility 30 min post-treatment in rats exposed to 21 days of corticosterone administration | N/A |
| Koike et al., 2013b | Male ICR (5 weeks) and male C57BL/6j (9 weeks) | Ketalar® Sankyo Yell Pharmaceutical Co., Ltd. 30 mg/kg i.p. | Ketamine decreased immobility in the FST & latency to feed in the NSF at 30 min and 24 h post-injection. K252a prevented ketamine's effects at 24 h. | N/A |
| Muller et al., 2013 | Male Sprague Dawley rats (330–400 g) | Fort-Dodge (Pfizer CT), USA. 15 mg/kg (i.p.) | Reduced immobility in FST 2 h post-injection | Increased p-αCamKII and decreased SNARE complex expression 1– 4 h post-injection. No effect on GSK-3 activity. Protracted increased in synapsin expression1 h to 7 days post-injection |
| Walker et al., 2013 | CD-1 mice (6 wks. old) and C57BL/6J mice (12 weeks old) | Fort Dodge Animal Health 6 mg/kg (i.p.) | Ketamine co-administered with LPS but not pretreatment 24 h prior blocked LPS-induced immobility in FST and anhedonia in the SPT. 10 h post LPS, ketamine administration reversed the anhedonia in SPT, this was blocked by NBQX | Ketamine did not block the LPS-induced increases in kynurenine metabolites, cytokines or BDNF expression at 6–28 h |
| Iijima et al., 2012 | C57Bl/6J mice (9 weeks) | Sigma-Aldrich 30 mg/kg (i.p.) | Latency to feed in the NSF was reduced at 30 min and 24 h post-injection. Rapamycin reversed the 24 h reduction in NSF latency | N/A |
| Liu et al., 2012 | BDNF knockin mice, (Val66Met SNP) Val/Met, Met/Met and Val/Val (WT) 6–8 months | Hospira Inc. 10 mg/kg (i.p.) | 24 h post-injection the AD effects of ketamine in the FST were blocked in Met/Met mice | Met/Met knockin mice are insensitive to the molecular effects of ketamine on spine head diameter and spine length modulated in WT mice |
| Yang et al., 2012 | Male Wistar rats (180–220 g) | Gutian Pharmaceutical CO. Ltd., Fuijan, China 10 mg/kg (i.p.) | Reduced immobility in FST 30 min post-injection | Increased mTOR phosphorylation in HC and PFC |
| Yang et al., 2013b | Male Wistar rats (200–300 g) | Gutian Pharmaceutical CO. Ltd., Fuijan, China 5–15 mg/kg (i.p.) | Dose-dependent reduction in immobility in the FST 30 min post-injection | Increased BDNF levels in the HC following 10 and 15 mg/kg. Dose dependent increase in phosphorylated mTOR levels in HC |
| Wang et al., 2011 | Male Wistar rats (60 days old) | Sigma-Aldrich 15 mg/kg (i.p.) | Decreased immobility in the FST 60 min post-injection | Increased BDNF expression and decreased phosphorylation of GluR1 (Ser845) in HC 60 min post-injection |
| Beurel et al., 2011 | WT and GSK-3 Knock in mice | 10 mg/kg (i.p.) | AD effects in LH in WT but not GSK-3 knock-in mice | Increased pGSK-3β (CTX and HC) 30 and 60 min post-injection |
| Koike et al., 2011a | Male ICR mice (25–35 g) | Sigma-Aldrich 3–30 mg/kg (i.p.) | Ketamine reduced immobility in the TST 24 h post 30 mg/kg injection. Rapamycin reversed the ketamine-induced reduction in TST immobility | N/A |
| Reus et al., 2011 | Male Wistar rats (60 days old) | Fort Dodge Animal Health—0.1 g/ml injectable solution, 5–10 mg/kg | Immobility in the FST was reduced at 60 min postinjection by 10 mg/kg only | Ketamine 5 mg/kg increased the expression of BDNF, CREB, and PKC phosphorylation in the PFC. 5mg/kg increased BDNF in the HC and Amg. 10 mg/kg decreased BDNF in the PFC, HC, and Amg. 10 mg/kg increased CREB expression and PKC phosphorylation in the PFC |
| Li et al., 2010 | Male Sprague Dawley rats (150–250 g) | Sigma-Aldrich 10 mg/kg (i.p.) | Ketamine produced AD effects in the FST, LH and NSF test 24 h post-injection, blocked by rapamycin | Ketamine 10 mg/kg activated mTOR, ERK, and PKB/Akt signaling, blocked by NBQX, Ketamine 10 mg/kg increased expression of certain synaptic proteins at 2, 6, and 72 h post-injection, blocked by rapamycin |
| Ghasemi et al., 2010 | Male NMRI mice (23–30 g) | Sigma-Aldrich 0.5–5 mg/kg (i.p) | Ketamine reduced immobility in the FST 45 min post-injection (2 and 5 mg/kg) | N/A |
| Cruz et al., 2009 | Male Swiss mice (25–35 g) | Sigma-Aldrich 6.35–50 mg/kg (i.p.) | 12.5, 25, and 50 mg/kg ketamine reduced immobility in the FST 30 min post-injection. Only 50 mg/kg ketamine reduced immobility in the TST | N/A |
| Engin et al., 2009 | Male Sprague-Dawley rats (180–360 g) | 10–50 mg/kg (i.p.) | Ketamine (50 mg/kg) increased the % of open arm entries in the EPM. Both doses decreased immobility in the FST 30 min post-injection | N/A |
| Rezin et al., 2009 | Male Wistar rats (300 g) | Fort Dodge Animal Health 15 mg/kg (i.p.) | Ketamine did not reverse the CMS-induced reduction in consumption of sweet food | Ketamine reversed the CMS-induced reductions in mitochondrial respiratory chain enzymes |
| Garcia et al., 2008a | Male Wistar rats (60 days old) | Fort Dodge (Brazil) 5, 10, and 15 mg/kg (i.p.) | 1 h post-injection ketamine (5 & 10 mg/kg) significantly reduced immobility in the FST | BDNF increased in the HC following ketamine injection (15 mg/kg) |
| Hayase et al., 2006 | Male ICR mice (60–90 days old) | Sankyo Co., Ltd. Tokyo, Japan 30–1.0 mg/kg (i.p.) | Ketamine increased the latency to immobility in the FST and was anxiolytic in the EPM at both doses 60 and 120 min post-injection | N/A |
| Rosa et al., 2003 | Swiss mice male and female (30–40 g) | Sigma-Aldrich 5 mg/kg (i.p.) | Ketamine reduced immobility in the TST 30 min post-injection | N/A |
| Mantovani et al., 2003 | Male Swiss mice 35–45 g) | 0.1 mg/kg (i.p.) | Ketamine reduced immobility in the TST 30 min post-injection | N/A |
This table outlines studies that have assessed the antidepressant-like effects of ketamine at 30 min to 24 h post-administration in commonly used behavioral tests. Molecular alterations of relevance to ketamine's molecular mechanism of action are also reported. FST, forced swim test; TST, tail suspension test; LH, learned helplessness; NSF, novelty suppressed feeding; SPT, sucrose preference test; EPM, elevated plus maze; AD, antidepressant; CMS, chronic mild stress; LPS, lipopolysaccharide; HC, hippocampus; CTX, cortex; Amg, amygdala; mPFC, medial prefrontal cortex; WT, wild type.