TABLE 1.
Summary of cognitive deficits induced by chemotherapeutic drugs in preclinical animal models of chemotherapy-induced cognitive impairment (CICI).
| Chemotherapeutic drug | Animal model | Regime | Cognitive impairments observed | References |
|---|---|---|---|---|
| Cyclophosphamide (CPA) | Young adult male ICR mice | One i.p. administration (40 mg/kg) | • CPA induced deficits in memory retention in the PAT and the NOR 12 h after administration | Yang et al. (2010) |
| • These CPA-related effects on cognition were not observed 10 days after drug administration | ||||
| Young adult male ICR mice | Weekly i.p. administration for 4 consecutive weeks (80 mg/kg per administration) | • Learning deficiencies in the PAT. | Hou et al. (2013) | |
| • Impairment of spatial memory in the Y-maze | ||||
| Young adult male athymic nude rats | Weekly i.p. administration for 5 consecutive weeks (50 mg/kg per administration) | • CPA administration caused an impairment of spatial memory in the NLR. | Christie et al. (2012) | |
| • In the FC paradigm, CPA caused a decrease of freezing upon re-exposure to the context, but not to the cue | ||||
| Oxaliplatin (OXA) | Male and female hooded Wistar rats | One i.p. administration (6 mg/kg) | • Male and female animals treated with OXA exhibited a deficit of working memory in the NOR. | Johnston et al. (2017) |
| • OXA induced a significant impairment of spatial memory in the NLR. | ||||
| • In the FC paradigm, OXA impaired the renewal of extinguished fear conditioning for up to 19 days after administration | ||||
| Male Sprague-Dawley rats | One i.p. administration (12 mg/kg) | • OXA administration induced an impairment in the renewal of extinguished fear in the FC paradigm | Sharpe et al. (2012) | |
| Male hooded Wistar rats | Weekly i.p. administration for 3 consecutive weeks (0.6, 2 and 6 mg/kg per administration) | • Only the highest dose of OXA (6 mg/kg) induced a gradual deterioration of the recognition memory in the NOR. This impairment became appreciable 4 months after and lasted up to 11 months | Fardell et al. (2015) | |
| • In the NLR the lower doses of OXA (0.6 and 2 mg/kg) induced a deficit of spatial memory 15 and 30 days after treatment, although this deleterious effect was not observed 4 and 11 months after OXA administration | ||||
| • The highest dose (6 mg/kg) induced a long lasting (up to 11 months after administration) deficit of spatial memory in the NLR. | ||||
| Cisplatin | Infant and adolescent male Sprague-Dawley rats | Weekly i.p. administration for 5 consecutive weeksd (2 mg/kg per administration) | • Cisplatin induced in infant and adolescent animals an impairment of the recognition memory in the NOR. | John et al. (2017) |
| • Only adolescent animals exhibited an impairment of spatial memory in the NLR. | ||||
| • In the FC paradigm, cisplatin impaired contextual memory, but not cued memory, of infant and adolescent animals | ||||
| 5-Fluorouracil (5-FU) | Young adult male C57BL/6 J mice | One i.p. administration (75 mg/kg) | • 5-FU caused short-term (2–12 weeks) impairments of spatial memory in the NLR and the Barnes maze. Likewise, 5-FU impaired recognition memory in the NOR. | Seigers et al. (2015) |
| • In the long term (15–25 weeks) only the spatial memory impairment in the NLR persisted | ||||
| Methotrexate (MTX) | Male Sprague-Dawley rats | One i.p. administration (20 mg/kg) | • Animals treated with MTX exhibited in the short-term deficits of memory retention in the PAT and an impairment of spatial memory in the Y-maze | Shalaby et al. (2019) |
| Infant female C57BL/6 J mice | One i.p. administration (20 mg/kg) | • Administration of MTX during infancy induced in the adulthood an impairment of spatial memory in the Morris water maze | Elens et al. (2019) | |
| Young adult male Long Evans rats | - One i.t. administration (0.5 mg/kg) | • Both administration schedules of MTX induced a deficit in recognition and spatial memory measured by the NOR and the NLR respectively | Vijayanathan et al. (2011) | |
| - Four i.t. administrations over 10 days (0.5 mg/kg per administration) | • Repeated MTX administration induced a longer deleterious effect on cognition than the single administration protocol | |||
| Infant male and female Swiss-Webster mice | Daily i.p. administration for 3 consecutive days (2 mg/kg per administration) | • Infant administration of MTX induced in the adolescence an impairment of recognition memory in the NOR. | Bisen-Hersh et al. (2013) | |
| Paclitaxel | Young adult male Sprague-Dawley rats | Four i.p. administrations every 2 days (2 mg/kg per administration) | • Impairment of spatial memory in the Morris water test | (Li et al., 2017), (Li et al., 2018) |
| Young adult male C57BL/6 J mice | One i.p. administration (33 mg/kg) | • Paclitaxel induced in the short (2–12 weeks) and the long term (15–25 weeks) an impairment of spatial memory in the NLR. | Seigers et al. (2015) | |
| Doxorubicin (DOX) | Young adult male C57BL/6 J mice | One i.v. administration (5 or 10 mg/kg) | • The lowest dose (5 mg/kg) impaired spatial memory in the NLR. | Seigers et al. (2015) |
| • The highest dose (10 mg/kg) induced an impairment of the recognition memory in the NOR and the spatial memory in the NLR and the Barnes maze | ||||
| Young adult male Wistar rats | Four i.p. administrations every 2 days (2 mg/kg per administration) | • DOX caused an impairment of spatial memory in the Morris water maze and memory retention in the PAT. | Park et al. (2018) | |
| Young adult male Wistar rats | One administration every 5 days over 50 days (2.5 mg/kg) | • DOX impaired recognition memory in the NOR. | Verma et al. (2017) |
- Chemotherapeutic agents: 5-FU, 5-Fluorouracil; CPA, cyclophosphamide; DOX, doxorubicin; MTX, methotrexate; OXA, oxaliplatin.
- Type of administration: i.p., intraperitoneal; i.t., intrathecal; i.v., intravenous.
- Behavioural test: FC, fear conditioning; NLR, novel location recognition test; NOR, novel object recognition test; PAT, passive avoidance test.