Table 2.

Summary of the cognitive-impairing effects of ketamine and their molecular correlates. Male adolescent and adult rodents are more sensitive to ketamine-induced impairments in memory. Ovarian hormones protect against ketamine-induced cognitive impairments.

Sex	Age	Dose	Treatment Regimen	Stress	Behavioral response	Molecular effect	References
Male	Adult	5 mg/kg	sub-chronic	NS	n/a	↑ CA3 caspace 3 activation	(Majewski-Tiedeken et al., 2008)
					↓ PPI	↑ HPC oxidative stress	(Celia Moreira Borella et al., 2016)
					↓ y-maze
		10 mg/kg	acute	NS	↓ 5-CSRTT time	n/a	(Nikiforuk and Popik, 2014a, Nikiforuk and Popik, 2014b)
				CUS	rescued ASST deficit	n/a	(Nikiforuk and Popik, 2014a, Nikiforuk and Popik, 2014b)
		20 mg/kg	chronic	NS	↑ radial arm maze latency	↓ HPC EAAT2 expression	(Featherstone et al., 2012)
Female	Adult	5 mg/kg	sub-chronic	NS	↑ PPI in proestrous	n/a	(Celia Moreira Borella et al., 2016)
					↓ PPI in diestrous
					↓ y-maze in proestrous
					↓ y-maze in diestrous
		10 mg/kg	acute	NS	↓ PPI in OVX females	n/a	(van den Buuse et al., 2015)
					↑ PPI in E2+P4 females
Male	Adolescent	5 mg/kg	sub-chronic	NS	no effect on PPI	n/a	(Celia Moreira Borella et al., 2016)
					↓ y-maze
		20 mg/kg	chronic	NS	↑ radial arm maze latency	↓ HPC EAAT2 expression in adulthood	(Nagy et al., 2015; Dodman et al., 2015)
					↑ SIT duration in adulthood	rescued with EAAT2 antagonist
		25 mg/kg	acute	NS	↓ NOR	↓ HPC LTD	(Silvestre de Ferron et al., 2015)
Female	Adolescent	5 mg/kg	sub-chronic	NS	no effect (PPI)	n/a	(Celia Moreira Borella et al., 2016)
					no effect (y-maze)

(NS= non-stressed; CUS = chronic unpredictable stress; PPI = pre-pulse inhibition; 5-CSRTT = 5 choice serial reaction time test; ASST = attentional set-shifting task; OVX = ovariectomized; E2 = estrogen; P4 = progesterone; SIT = social interaction test; NOR = novel object recognition; HPC = hippocampus; EAAT2 = excitatory amino acid transporter 2; LTD = long-term depression.