Table 1.

Behavioral abnormalities that match schizophrenia symptoms and their treatment

Model	Positive symptoms	Negative symptoms	Cognitive symptoms	Antipsychotic treatment	MN treatment
DISC1 (129S6/SvEv mouse strain)	Hyperlocomotion, PPI deficits.27	Increased immobility in the forced swimming and tail suspension test.27	No deficits in the Y-maze test for working memory.27	ND	ND
NMDA antagonists	Hyperlocomotion, PPI deficit (not sustained, only upon repeated administration of any of the NMDA antagonists), and latent inhibition deficits.37–56	Social withdrawal, forced swimming immobility, increased anxiety-like behavior.37–56	Deficits in: novel object recognition, attentional set shifting, and T-maze delayed alternation and reversal learning along with working memory and visuospatial memory deficits in the Morris’s water maze.37–56	TAP had no effect on the negative symptoms. Haloperidol reverses hyperlocomotion and novel object recognition deficits. AAP reverses all the mentioned deficits.37–56	Pretreatment with MN, prior to NMDA-antagonist injection, prevents the outbreak of positive cognitive and negative manifestations. Treatment with MN post NMDA-antagonist administration reverts the latter symptoms.38,46,64–66
nVHL	PPI deficits, drug-induced hyperlocomotion, increased aggression, higher risk taking behavior, and disrupted latent inhibition.83,85–88	Social withdrawal enhanced immobility in forced swimming test when administered PCP.84	Deficits in working and spatial memory.85,89,90	AAP have no effect on social withdrawal but reversed amphetamine-induced hyperlocomotion.86,91 TAP restored increased aggression.88 AAP are able to rescue PPI deficits, but not TAP.88	MN treatment prior to lesion prevented the phenotype outbreak completely.95 Chronic MN treatment starting at P42 rescued all behavioral abnormalities in the LPS induced nVHL.102
PolyI:C	Drug-induced hyper-locomotion, deficits in PPI, and latent inhibition.116,117	Social withdrawal, decreased sucrose preference, increased immobility in the forced swimming test, and tail suspension test.122,144–146	Deficits in: working memory, intentional set shifting along with spatial memory deficits, and impaired object-in-place recognition memory.119,145,147,148	AAP reverses deficits in working memory and latent inhibition, the latter also rescued by TAP. No tests have been carried for screening on the negative symptoms.143,149	MN restored PPI deficits and social withdrawal. No test has been carried out on other behavioral abnormalities.16,158
LPS	Psychostimulant-induced hyperactivity, PPI deficits.175,181,182	Increased despair in the forced swimming test. Decreased social behavior and increased anxiety.176–178,180	Impaired object-recognition memory and spatial learning.175,179	TAP and AAP reverse the PPI deficits and chlorpromazine the drug-induced hyperactivity.171,183	ND

Notes: The table summarizes the main behavioral abnormalities that best match positive, negative, and cognitive symptoms of schizophrenia displayed by the animal models described in this review. Moreover, the table reports the effect of present antipsychotic treatment and anti-inflammatory minocycline intervention on the behavioral manifestations.

Abbreviations: MN, minocycline; DISC1, disrupted in schizophrenia-1; NMDA, N-methyl-D-aspartate; PCP, phencyclidine; TAP, typical antipsychotics; AAP, atypical antipsychotics; nVHL, neonatal ventral hippocampal lesion; PPI, prepulse inhibition; P42, postnatal day 42; ND, not determined; LPS, lipopolysaccharide.