Table 2. Recent studies using behavioral paradigms that measure negative symptoms of schizophrenia in rodent models.

Paradigm	Animal Model	Experimental Manipulation	Results	References
Forced swim test	Developmental	LPS-treated NMRI mouse offspring	↑ increased immobility	[97]
	Genetic	En2 null mutant mice	↑ increased immobility	[98]
		EPRAP KO mice	↑ increased immobility	[100]
		NCS-1 KO mice	↑ increased immobility	[105]
		NT KO mice	↑ increased immobility	[104]
		Heterozygous reeler mice + corticosterone	↑ increased immobility	[99]
		GRIA1 KO mice	↓ decreased immobility	[106]
		ALK KO homozygous mice	↓ decreased immobility	[103]
		GCLM KO mice	↓ decreased immobility	[101]
		DBA/2J mice	↓ decreased immobility	[102]
		PTPRG KO mice	↓ decreased immobility	[107]
		Grin1(Rgsc174)/Grin1+ mice	NE	[108]
	Pharmacological	Chronic administration of ketamine in mice	↑ increased immobility	[109]
		Subchronic treatment with ketamine in mice	↑ increased immobility	[110]
		13-day treatment with MK-801 in mice	↑ increased immobility	[112]
		15-day treatment with MK-801 in mice	↑ increased immobility	[111]
		PCP treatment in mice	↑ increased immobility	[113]
Tail suspension test	Developmental	LPS-treated NMRI mouse offspring	↑ increased immobility	[97]
		Prenatal LPS-exposed mice	↑ increased immobility	[122]
	Genetic	SREBP1c KO mice	↑ increased immobility	[47]
		Forebrain-specific NCAM-deficient mice	↑ increased immobility	[123]
		Male MB-COMT deficient mice	↑ increased immobility	[124]
		NCS-1 KO mice	↑ increased immobility	[105]
		NT KO mice	↑ increased immobility	[104]
		GRIA1 KO mice	↓ decreased immobility	[106]
		DBA/2J mice	↓ decreased immobility	[102]
		Grin1(Rgsc174)/Grin1+ mice	NE	[108]
	Pharmacological	Subchronic treatment with ketamine in mice	↑ increased immobility	[110]
		Chronic administration of ketamine in mice	NE	[119]
		Subchronic PCP administration in mice	NE	[125]
Sucrose preference test	Developmental	Viral mimic Poly(I:C)-induced MIA mouse offspring	↓ decreased preference	[129]
		Perinatal L-Dopa treatment in male juvenile mice	↓ decreased preference	[46]
	Genetic	CD2 KO mice	↓ decreased preference	[130]
		G72/G30 Tg mice	↓ decreased preference	[131]
		Grin1(ΔPV) mice + MK-801	↓ decreased preference	[132]
		Grik4 KO mice	↑ increased preference	[133]
		Ahi1 +/- KO mice + chronic unpredictable stress	NE	[134]
		GluA1 KO mice	NE	[135]
		NRG1 mutant mice + stress	NE	[136]
	Pharmacological	JNJ chronic administration in mice	↓ decreased preference	[137]
Three-chamber sociality test	Genetic	Brain-specific CRMP 2 knockout (cKO) mice	↓ decreased social interaction	[52]
		Pcm1+/− mice	↓ decreased social interaction	[140]
		SREBP1c KO mice	↓ decreased social interaction	[47]
		CPB-K mice	↓ decreased social interaction	[141]
		Glu-CB1(-/-) female mice	↓ decreased social interaction	[142]
		Reelin deficiency + corticosterone in male mice	↓ decreased social interaction	[71]
		Sarm1 knockdown mice	↓ decreased social interaction	[143]
		V1aR KO mice	↓ decreased social interaction	[144]
		Type III NRG1+/- male mice from mutant fathers	↑ increased social interaction	[58]
		Selective knockdown of PLC-β1 in mPFC of male mice	NE	[59]
		NRG1 mutant mice	NE	[146]
	Pharmacological	Ketamine treatment in mice	↓ decreased social interaction	[145]
		PCP treatment in mice	↓ decreased social interaction	[113]
		Administration of Catha edulis forsk extract	↓ decreased social interaction	[60]
Elevated plus maze	Genetic	Nlgn2 R215H knock-in homozygous mice	↑ increased anxiety-like behavior	[73]
		Heterozygous Ank3 KO mice	↑ increased anxiety-like behavior	[152]
		Female DISC1(D453G) mice	↑ increased anxiety-like behavior	[153]
		Kynurenine 3-monooxygenase-deficient mice	↑ increased anxiety-like behavior	[154]
		NAc-TMEM mice	↑ increased anxiety-like behavior	[80]
		FFAR1-/- female mice	↓ decreased anxiety-like behavior	[155]
		Forebrain knockout of DNMT1 in mice	↓ decreased anxiety-like behavior	[156]
		CRMP2 deficient mice	↓ decreased anxiety-like behavior	[157]
		Mutant DISC1 male mice	NE	[158]
		Pcm1(+/-) mice	NE	[140]
		Type III NRG1+/- male mice from mutant fathers	NE	[58]

Abbreviations: Ahi1 = Abelson helper integration site 1; ALK = anaplastic lymphoma kinase; Ank3 = ankyrin 3; CD2 = cyclin-D2; CRMP2 = collapsin response mediator protein 2; DISC1 = disrupted-in-schizophrenia 1; DNMT1, DNA methyltransferase 1; En2 = engrailed-2; EPRAP = EP4 receptor-associated protein; FFAR1 = free fatty acid receptor 1; GCLM = glutamate-cysteine ligase modifier; GLAST = glial glutamate and aspartate transporter; GluA1 = glutamate A1; Glu-CB1 = cannabinoid receptor type 1 in glutamergic neurons; GRIA1 = glutamate ionotropic receptor AMPA type subunit 1; Grik4 = glutamate receptor, ionotropic, kainate 4; Grin1 = glutamate ionotropic receptor NMDA type subunit 1; JNJ = JNJ-28871063; KO = knockout; L-dopa = levodopa; LPS = lipopolysaccharide; MB-COMT = membrane-bound catechol-O-methyltransferase; MIA = maternal immune activation; mPFC = medial prefrontal cortex; NAc-TMEM mice = Tmem168 vector injected into the NAc of C57BL/6J mice; NCAM = neural cell adhesion molecule; NCS-1 = neuronal calcium sensor; Nlgn2 R215H = missense mutation R215H of neuroligin 2; NMRI = Naval Medical Research Institute; NRG1 = neuregulin-1; NT = neurotensin; Pcm1 = pericentriolar material 1; PCP = phencyclidine; PLC-β1 = phospholipase C-β1; poly(I:C) = polyinosinic-polycytidylic acid; PTPRG = receptor protein tyrosine phosphatase gamma; SARM1 = sterile alpha and TIR motif-containing 1; SREBP1c = sterol regulatory element-binding protein 1c; Tg = transgenic; V1AR = vasopressin receptor 1A; NE = no effect.