Table 2.

Summary of the effects of calcium/calmodulin-dependent kinases II and IV genetic manipulation in rodents.

	CaMKII				CaMKIV
Genetic Manipulation	Behavioral Assay	Effect in Rodents	Reference	Genetic Manipulation	Behavioral Assay	Effect in Rodents	Reference
Homozygous CaMKIIα knockout	FST	no changes	[116]	CaMKIV knockout	FST, TST	no changes	[153]
Heterozygous CaMKIIα knockout	FST	depressive-like state	[118]	homozygous CaMKIV knockout	FST, TST	depressive-like state	[154]
CaMKIIβ overexpression	FST, SPT	antidepressant-like effect	[15,119]	-	-	-	-
CaMKIIβ knockdown (hippocampus) in UCMS rats	SPT, FST	antidepressant-like effect	[119]	-	-	-	-
CaMKIIα knockdown	OFT	anxiolytic-like effect	[155]	homozygous CaMKIV knockout	EPM, LDT, acoustic startle and prepulse inhibition	anxiolytic-like effect	[153,156]
Hetero- and homozygous CaMKIIα knockout	FC	anxiolytic-like effect	[157]	homozygous CaMKIV knockout	marble-burying test, light dark box	anxiolytic-like effect	[158]
Hetero- and homozygous CaMKIIβ knockout	EPM, OFT	anxiolytic-like effect	[40]	hetero- and homozygous CaMKIV knockout + nicotine dependence and withdrawal	conditioned place preference test	anxiolytic-like effect (during withdrawal)	[159]
CaMKIIα overexpression	OFT, EZM, RT	anxiety-like state	[160]
CaMKIIα-T286 mutant mice	Morris water maze	memory impairment	[161]	homozygous CaMKIV knockout	FC		[158,162]
CaMKIIα-T286 mutant mice	PA, cued FC	memory impairment	[163]	homozygous CaMKIV knockout	eyeblink conditioning test, vestibulo-ocular reflex testing		[164,165]
Heterozygous CaMKIIα knockout	RAM, delayed alternation task	working memory impairment	[13,118]	homozygous CaMKIV knockout	Morris water maze, Barnes maze, RAM		[166]
Heterozygous CaMKIIα knockout	FC	memory impairment	[157,167]	CaMKIV knockout	Barnes maze, RAM, PA	no changes	[153]
Heterozygous CaMKIIα knockout	Morris water maze	memory impairment	[168]	CaMKIV knockout	FC	memory impairment	[153]
CaMKII-Asp-286	Barnes maze, FC	spatial memory impairnent, no effect on contextual memory	[169]	heterozygous CaMKIVα knockout	Morris water maze, FC	memory impairment	[113]
Heterozygous CaMKIIα knockout	Morris water maze, FC	long-term memory impairment	[170]	CaMKIV overexpression	FC	memory enhacement	[171,172]
Kinase-dead CaMKIIα (K42R)-knockin	Morris water maze, FC	spatial and contextual memory impairment		CaMKIV overexpression	PA, social recognition test		[112]
Hetero- and homozygous CaMKIIβ knockout	NOR	memory impairment	[40]

CaMKII—calcium/calmodulin-dependent kinase II, CaMKIV—calcium/calmodulin-dependent kinase IV, EPM—elevated plus maze test, EZM—elevated zero maze, FC—fear conditioning, FST—forced swim test, LDT—light/dark test, NOR—novel object recognition task, OFT—open field test, PA—passive avoidance, RAM—radial arm maze, RT—rotarod test, SPT—sucrose preference test, TST—tail suspension test, UCMS – unpredictable chronic mild stress.