Table 1. Behavioral effects of morphine and heroin in opioid receptor and peptide knockout mice.

Data are shown for each knockout (gene KO) mouse line. Behavioral tests are detailed in the Box. Unchanged: no genotype effect; increased: KO shows higher response compared to wild-type (WT); decreased: KO shows lower response compared to WT; abolished: no response in KO. CPP: Conditioned Place Preference; d: day; SA: self-administration; VTA: ventral tegmental area; FR: fixed ratio; PR: progressive ratio.

Gene KO	Drug of abuse	Behavioral test	Drug of abuse dose, route	Genotype effect	Ref
mu	morphine	CPP	3 mg/kg, s.c.	abolished	Matthes et al., 1996
		CPP	10 mg/kg, s.c.	abolished	Sora et al., 2001
		CPP	10 mg/kg, s.c.	abolished	Nguyen et al., 2012a
		CPP	10 mg/kg, s.c.	abolished	Nguyen et al., 2012b
		+ challenge on d14	5 mg/kg, s.c.	abolished
		SA	2 or 4 mg/0.2mL, i.c.v. FR1	lower than saline groups	Becker et al., 2000
		SA	0.1 or 0.3 mg/kg/injection, i.v. FR4	abolished	Sora et al., 2001
		VTA SA	50 or 100 ng/infusion	abolished	David et al., 2008
		withdrawal	20 to 100 mg/kg, i.p. (2x/d, 5d)	abolished	Matthes et al., 1996
	heroin	CPP	1 mg/kg, i.p.	abolished	Contarino et al., 2002
delta	morphine	CPP preferred side	10 mg/kg, s.c.	abolished	Chefer et al., 2009
		CPP non-preferred side	10 mg/kg, s.c.	unchanged
		CPP drug free state	5 mg/kg, s.c.	abolished	Le Merrer et al., 2011
		CPP under morphine	5 mg/kg, s.c.	unchanged
		CPP without cue	10 mg/kg, s.c.	abolished	Le Merrer et al., 2012
		CPP with cue	5, 10 and 20 mg/kg, s.c.	unchanged/restored
		SA	0.25 or 0.5 mg/kg/infusion, i.v. FR1	unchanged	Le Merrer et al., 2011
			0.25 mg/kg/infusion, i.v. PR	unchanged
			0.5 mg/kg/infusion, i.v. PR	increased
		VTA SA	50 ng/infusion	unchanged	David et al., 2008
		withdrawal	75 mg, pellet (3d)	unchanged	Nitsche et al., 2002
kappa	morphine	CPP	1 mg/kg, s.c.	unchanged	Simonin et al., 1998
		withdrawal	20 to 100 mg/kg, i.p. (2x/d, 6d)	abolished	Simonin et al., 1998
βend	morphine	CPP	10 mg/kg, s.c.	increased	Skoubis et al., 2005
		CPP	5 mg/kg, s.c.	unchanged	Niikura et al., 2008
pEnk	morphine	CPP	10 mg/kg, s.c.	unchanged	Skoubis et al., 2005
		withdrawal	75 mg, pellet (3d)	increased	Nitsche et al., 2002
		withdrawal jumping	20 mg/kg, s.c. (1 inj)	decreased	Shoblock & Maidment, 2007
			100 mg/kg, s.c. (2d)	abolished
pDyn	morphine	CPP	5 mg/kg, s.c.	unchanged	Zimmer et al., 2001
		CPP	3.5 mg/kg, s.c.	unchanged	Mizoguchi et al., 2010
		withdrawal	20 to 100 mg/kg, i.p. (2x/d, 5d)	unchanged	Zimmer et al., 2001