. 2018 Sep 21;9:166–175. doi: 10.1016/j.ynstr.2018.09.001

Table 1.

Summary of the addictive properties of low-dose ketamine in rodents and molecular correlates. Female adolescent and adult rodents are more sensitive to the locomotor-activating effects of ketamine. The reinforcing properties of ketamine in females are mediated by the presence of ovarian hormones.

Sex	Age	Dose	R.O.A.	Treatment Regimen	Behavioral Response	Molecular Change	References
Male	Adult	100 μg per inf	i.v.	1x/4 days	↑ FR1 self-administration	n/a	(Wright et al., 2017)
		100 μg per inf	i.v.	1x/4 days	↑ cue-induced reinstatement	n/a	(Wright et al., 2017)
		2.5 mg/kg	i.p.	1x/2 days	no change	↑NAc ΔfosB	(Schoepfer et al., 2017)
		2.5 mg/kg	i.p.	Weekly	no change	↑ NAc shell spines	(Strong et al., 2017)
		5 mg/kg	i.p.	Daily	↑ locomotor sensitization	n/a	(Botanas et al., 2015)
				Daily	↑ CPP	n/a	(Botanas et al., 2015)
				1x/2 days	↑ locomotor sensitization	↑NAc ΔfosB	(Schoepfer et al., 2017)
				Weekly	↑ locomotor sensitization	↑ NAc ΔfosB	(Strong et al., 2017)
						↑ NAc GluA1
						↑ NAc BDNF
						↑ NAc CaMKIIα
						↑ NAc shell spines
		10 mg/kg	i.p.	Daily	↑ locomotor sensitization	n/a	(Wiley et al., 2008)
				Daily	↑ CPP	n/a	(Li et al., 2008)
				1x/2 days	↑ locomotor sensitization	↑ NAc ΔfosB	(Schoepfer et al., 2017)
				1x/2 days	↑ CPP	↑ NAc ΔfosB	(Schoepfer et al., 2017)
Female	Adult	100 μg per inf	i.v.	1x/4 days	↑ FR1 self-administration (proestrous)	n/a	(Wright et al., 2017)
					↑cue-induced reinstatement (proestrous)
					↓FR1 self-administration (diestrous)
					↓ cue-induced reinstatement (diestrous)
		2.5 mg/kg	i.p.	1x/2 days	no change	↑NAc ΔfosB	(Schoepfer et al., 2017)
		2.5 mg/kg	i.p.	Weekly	↑ locomotor sensitization (diestrous)	↑ NAc shell spines	(Strong et al., 2017)
		5 mg/kg	i.p.	1x/2 days	↑ locomotor sensitization	↑NAc ΔfosB	(Schoepfer et al., 2017)
				1x/2 days	↓ CPP	↑NAc ΔfosB	(Schoepfer et al., 2017)
				Weekly	↑ locomotor sensitization	↑ NAc GluA1	(Strong et al., 2017)
					↓ CPP (diestrous)	↑ NAc core spines
					↓ CPP (diestrous)	↑ NAc shell spines
		10 mg/kg	i.p.	Daily	↑ locomotor sensitization	n/a	(Wiley et al., 2011)
		10 mg/kg	i.p.	1x/2 days	↑ locomotor sensitization	↑NAc ΔfosB	(Schoepfer et al., 2017)
Male	Adolescent	10 mg/kg	i.p.	Daily	no change	n/a	(Wiley et al., 2007)
		20 mg/kg	i.p.	Daily	↑ locomotor sensitization no change in CPP	n/a	(Rocha et al., 2017)
		20 mg/kg	i.p.	Daily	↑ locomotor sensitization no change in CPP	n/a	(Parise et al., 2013)
Female	Adolescent	10 mg/kg	i.p.	Daily	↑ locomotor sensitization	n/a	(Wiley et al., 2011)

(inf = infusion; i.p. = intraperitoneal; CPP = conditioned place preference; NAc = nucleus accumbens; GluA1 = AMPA receptor 1; CaMKIIα = calcium calmodulin kinase II alpha).