Table 1.
Comparison of animal models of phencyclidine.
| Corresponding to SCZ | Dose/Regimen | Sex/Strain | Behavioral deficits | Structural and neurochemical changes | References |
|---|---|---|---|---|---|
| Positive | Acute (2.5–15 mg/kg) | Male Sprague-Dawley Rats | Hyperlocomotor activity, increased stereotypy and ataxia | Not tested | Sturgeon et al., 1979 |
| Acute (0.9–29 μmol/kg) or (0.5–10 mg/kg) | Male Wistar Rats | Decreased locomotor activity, increased stereotypy and ataxia | Not tested | Sams-Dodd, 1995, 1996 | |
| Subchronic (0.25–8 mg/kg for 5 days) or (0.9–29 μmol/kg for 3 days) | Male Wistar Rats | Hyperlocomotor activity, increased stereotypy and ataxia | Stereotyped behavior reversed by chronic clozapine administration | Sams-Dodd, 1995, 1996 | |
| Subchronic (5 mg/kg bi-daily for 7 days) | Male Sprague-Dawley Rats | Hyperlocomotor activity, increased sensitivity to amphetamine | Reduced prefrontal cortical DA utilization, prolonged hypoactivity of mesocortical DA neurons and hyper-responsivity of mesolimbic DA neurons | Jentsch et al., 1998 | |
| Subchronic (5 mg/kg for 3–14 days) | Male Sprague-Dawley Rats | Hyperlocomotor activity | Dose-dependent enhancement in amphetamine-induced DA release in the PFC | Balla et al., 2003 | |
| Negative | Acute (0.45–57 μmol/kg) | Male Wistar Rats | Decreased social behavior | Not tested | Sams-Dodd, 1995, 1996 |
| Subchronic (0.25–8.0 mg/kg for 5 days) or (0.9–29 μmol/kg for 3 days) | Male Wistar Rats | Concomitant reductions in the explorative and social behaviors | Social isolation reversed by chronic clozapine administration | Sams-Dodd, 1995, 1996 | |
| Subchronic (10 mg/kg for 14 days) | Male ddY mice | Increased time immobile in the FST | FST effect was reversed by atypical APDs, risperidone and clozapine | Noda et al., 1995 | |
| Subchronic (2 mg/kg bi-daily for 7 days) | Male hooded-Listar Rats | Disturbances in social interaction | Reduced PV+ neurons in the hippocampus with significant reductions localized to the CA1 and DG regions of the hippocampus | Jenkins et al., 2008 | |
| Subchronic (5 mg/kg bi-daily for 7 days) | Male C57/BL6 WT mice | Partial deficits in social behavior | Not tested | Brigman et al., 2009 | |
| Cognition | Acute (0.25, 0.75, 1.5, 10 mg/kg) | Male and female Sprague Dawley Rats | Decreased sensorimotor gating | PCP increases brain metabolism in areas of cortex, basal ganglia, and thalamus; enhances norepinephrine release and inhibits striatal synaptosomal DA | Martinez et al., 1999 |
| Acute (0.5 mg/kg, 1 mg/kg) | Male ddY mice | Impaired latent learning in a one-trial water-finding task | Sigma1 receptor ligands attenuated the PCP-induced latent learning impairment | Noda et al., 2001 | |
| Acute (1.0, 1.5 mg/kg) | Female Hooded Listar Rats (socially isolated from P21) | Impaired reversal task performance, increased locomotor activity from isolated rats compared to socially reared rats | Atypical APD (ziprasidone) reversed impairments caused by PCP | Abdul-Monim et al., 2003 | |
| Acute (2.58 mg/kg) | Male hooded Long-Evans Rats | Deficits in attentional set-shifting | Altered zif268 mRNA expression in the infralimbic cortex and PV mRNA expression in the dorsal reticular nucleus of the thalamus | Egerton et al., 2005 | |
| Acute (10 mg/kg on P7) | Male Sprague Dawley Rats | Not tested | Loss of PV containing neurons from primary somatosensory, motor, and retrosplenial cortices | Wang et al., 2008 | |
| Subchronic (10 mg/kg for 10 days, 5 mg/kg bi-daily for 7 days) | Male Sprague-Dawley Rats | Impaired spatial delayed alternation task | Decreased basal DA utilization in the PFC | Jentsch et al., 1997b | |
| Subchronic (2 mg/kg bi-daily for 7 days) | Female hooded-Listar Rats | Enduring, persistent deficits in reversal learning | Cognitive deficits are attenuated by treating with atypical but not classical APDs | Abdul-Monim et al., 2006 | |
| Subchronic (2 mg/kg bi-daily for 7 days) | Female hooded-Listar Rats | Deficits in reversal learning | Reduced PV+ neurons in the hippocampus, frontal cortex with reduced in the motor area 1 (M1) and increases in motor area 2 (M2) region and cingulate cortex | Abdul-Monim et al., 2007 | |
| Subchronic (2 mg/kg bi-daily for 7 days) | Female hooded-Listar Rats | Deficits in novel object recognition test | Clozapine and risperidone attenuated PCP-induced impairments | Grayson et al., 2007 | |
| Subchronic (2.6 mg/kg for 5 days) | Male hooded Long-Evans Rats | Deficits in attentional set-shifting and sensorimotor gating | Transient metabolic alterations present across multiple brain regions | Egerton et al., 2008 | |
| Subchronic (2 mg/kg bi-daily for 7 days) | Male hooded-Listar Rats | Deficits in novel object recognition test | Reduction in PV+ neurons in the PFC with specific deficits observed in the prelimbic region | McKibben et al., 2010 | |
| Chronic intermittent exposure (5 mg/kg bi-daily for 5 days, 3 days after 10 days) | Male Sprague-Dawley Rats | No long-term impairment in T-maze alternation performance | Not tested | Stefani and Moghaddam, 2002 | |
| Chronic intermittent exposure(0.86 or 2.58 mg/kg for 5 days and post-8–26 days) | Male hooded Long-Evans Rats | Not tested | Metabolic hypofunction in PFC increase glutamate release; initial increase in glucose utilization or uptake, activating non-NMDARs | Cochran et al., 2003 | |
| Chronic intermittent exposure(2.6 mg/kg for 5 days and post-8–26 days) | Male hooded Long-Evans Rats | Deficits in attentional set-shifting | Transient metabolic alterations present across multiple brain regions | Egerton et al., 2008 |