Table 2.
Comparison of the effects of various subchronic PCP administration protocols on cognitive paradigms in rats and mice as indicated
| Dose | Species/Strain/Sex | Time of test | Behavioural test | Antipsychotic drug effect | Reference |
|---|---|---|---|---|---|
| Subchronic (2 mg·kg−1) | Rat/Lister hooded/♀ | >7 days | Deficit in reversal learning | Reversed by acute ASN, CLZ, OLZ, SRT, ZPD and repeated ASN, RSP and OLZ; no effect of acute HLP or CPM | (Abdul-Monim et al., 2006; Idris et al., 2010; McLean et al., 2010b) |
| 7 days | Deficit in novel object recognition | Reversed by acute CLZ, MLP, OLZ, RSP, SRT, but not HLP | (Grayson et al., 2007; Idris et al., 2010; Snigdha et al., 2010) | ||
| Subchronic (2 mg·kg−1) | Rat/Sprague-Dawley/♂ | 7 days | Deficit in reversal learning | (Jentsch and Taylor, 2001) | |
| Deficit in novel object recognition | No effect of concurrent RSP | (McKibben et al., 2010) | |||
| Subchronic (4.5 mg·kg−1) | Rat/Sprague-Dawley/♂ | 7 days | Deficit in performance in double Y-maze | (Beninger et al., 2010) | |
| Subchronic (5 mg·kg−1) | Rat/Lister hooded/♂ | 7 days | Deficit in episodic memory | No effect of CLZ | (Le Cozannet et al., 2010) |
| Deficit in attentional set shifting | Reversed by acute SRT, but not RSP or HLP | (Rodefer et al., 2005; Broberg et al., 2009; Goetghebeur and Dias, 2009) | |||
| Rat/Wistar/♂ | 72 h | Deficit in delayed alternation task | (Seillier and Giuffrida, 2009) | ||
| Mice/C57BL/6J/♂ | 7 days | No deficit in operant behaviour or reversal learning | (Brigman et al., 2009) | ||
| Chronic intermittent (2.6 mg·kg−1, 28 days) | Rat/Long-Evans/♂ | 72 h | Impaired attentional set shifting | (Egerton et al., 2008) | |
| 24 h | Deficit in novel object recognition | (Spano et al., 2010) | |||
| 3 days per week for 5 weeks (3 mg·kg−1) | Rat/Sprague-Dawley/♂ | 4 weeks | No effect on attentional set shifting | (Fletcher et al., 2005) | |
| Osmotic minipump (15 mg·kg−1·day−1, 14 days) | Rat/Lister hooded/♂ | 7 days | Impaired attentional set shifting | (Pedersen et al., 2009) | |
| 12 days (0.5–4 mg·kg−1) | Mice/C57Bl/6J/♂ | 15 min | Impaired spatial learning at low dose | Reversed by repeated CLZ, but not HLP | (Beraki et al., 2008) |
| 14 days (10 mg·kg−1) | Rat/Sprague-Dawley and Long-Evans/♂ | 48 h | Deficit in spatial delay alternation task (at longer delays) | (Jentsch et al., 1997b) (Marquis et al., 2007) | |
| Mice/ICR/♂ | 5 days | Deficit in novel object recognition | Reversed by acute and repeated ARP, but not HLP | (Nagai et al., 2009) | |
| Mice/C57BL/6J and Rat/Sprague-Dawley/♂ | 7 days | No deficit in spatial performance | (Li et al., 2003) | ||
| 10 days (with 2 day break) (10 mg·kg−1) | Mice/ICR/♂ | 14 days | Deficit in novel object recognition | Reversed by repeated QTP | (Tanibuchi et al., 2009) |
| 6 days (1.3 mg·kg−1) | Rat/Wistar/♂ | 30 min | Deficit in spatial learning and memory | Reversed by acute CLZ, SRT and RSP; no effect of HLP | (Didriksen et al., 2007) |
| 5 days (b.i.d. 5 mg·kg−1) | Rat/Sprague-Dawley/♂ | 9 days | No deficit in spatial delay alternation task (short delays) | (Stefani and Moghaddam, 2002) | |
| 5 days (2 mg·kg−1) | Rat/Wistar/♂ | 30 min | Deficit in attention, cognitive flexibility and speed of processing | Partially attenuated by chronic CLZ, but not QTP | (Amitai et al., 2007; Amitai and Markou, 2009b) |
Time of test indicates duration after the last PCP injection that the task was evaluated. Subchronic: PCP twice daily for 7 days, chronic intermittent: PCP once daily for 5 days followed by three times a week for 3 weeks.
Abbreviations: ARP, aripirazole; ASN, asenapine; CLZ, clozapine; CPM, chlorpromazine; HLP, haloperidol; MLP, melparone; OLZ, olanzapine; QTP, quetiapine; RSP, risperidone; SRT, sertindole; ZPD, ziprasidone. Note: As no current antipsychotic drugs reverse cognitive deficits seen in schizophrenia, the translational relevance of these observations in rodents is currently difficult to evaluate, only in future if cognitive enhancers are developed will the true predictive value of these tasks become apparent.