Table 1.

Time Point of KOR Antagonist Administration or Gene Ablation Relative to Exposure to Stressors

Stressor	Treatment (Method)	Treatment Time Relative to 1st Stressor	Behavioral Effect		Species, Strain	References
			TEST 1	TEST 2
BEFORE STRESSORS
Forced Swim	NorBNI, GNTI (ICV)	3d before	Not Determined	Decreased Immobility	Rats, CD	Pliakas et al., 2001 Mague et al., 2003
	NorBNI (IP)	1h before daily stress	No Effect	Decreased Immobility	Mice, C57Bl/6	McLaughlin et al., 2003; 2006a
			Decreased Immobility			Carey et al., 2009
	KOR −/−	N/A	No Effect	Decreased Immobility	Mice, C57Bl/6	McLaughlin et al., 2003; 2006a
				Not Determined	Mice, Hybrid 129SV/C57Bl/6	Filliol et al., 2003
	PDyn −/−	N/A	No Effect	Decreased Immobility	Mice, C57Bl/6	McLaughlin et al., 2003
	PDyn −/−	N/A	No Effect	Increased Immobility*	Mice, C57Bl/6	Wittmann et al., 2009
Social Defeat	NorBNI (IP)	1h before daily stress	No Effect	Decreased Social Defeat	Mice, C57Bl/6	McLaughlin et al., 2006b
	PDyn −/−	N/A
Stress-Induced Potentiation Cocaine-CPP	NorBNI (IP)	1h before daily stress	Blocked Stress-Induced Potentiation of Cocaine-CPP, No Effect Unstressed Mice		Mice, C57Bl/6	McLaughlin et al., 2003; 2006a; 2006b
	KOR −/−	N/A
	PDyn −/−	N/A
Stress-Induced Reinstatement of Cocaine-Seeking	JDTic (IG)	24h before stress	Decreased Stress-Induced Reinstatement, No Effect on Cocaine-Primed Reinstatement		Rats, Long-Evans	Beardsley et al., 2005
	Arodyn (ICV)	1h before stress			Mice, C57Bl/6	Carey et al., 2007
	NorBNI (IP)	1h before stress				Redila & Chavkin, 2008
	KOR −/− PDyn −/−	N/A
Stress-Induced	NorBNI (IP)	1h before daily stress	Decreased Deficit in NOR		Mice, C57Bl/6	Carey et al., 2009
Deficit Novel Object Recognition	PDyn −/−	N/A
Elevated Plus Maze	NorBNI, JDTic (IP)	48h before	Increased Open Arm Exploration		Rats, CD	Knoll et al., 2007
	PDyn −/−	N/A			Mice, C57Bl/6	Wittmann et al., 2009
	KOR −/−	N/A	No Effect		Mice, Hybrid 129SV/C57Bl/6	Simonin et al., 1998
Zero Maze	KOR −/−	N/A	No Effect; Also No Effect Y maze		Mice, Hybrid 129SV/C57Bl/6	Simonin et al., 1998
	PDyn −/−	N/A	Decreased Exploration		Mice, C57Bl/6	Bilkei-Gorzo et al., 2008
	NorBNI (IP)	3d before	No Effect		Rats, CD	Knoll et al., 2007
Open Field	NorBNI (IP) GNTI (IC)	48h before 20h before	Increased Center Exploration		Mice, C57Bl/6	Wittmann et al., 2009
	PDyn −/−	N/A
	KOR −/−	N/A	No Effect		Mice, Hybrid 129SV/C57Bl/6	Simonin et al., 1998
Light-Dark Test	PDyn −/−	N/A	No Effect		Mice, C57Bl/6	Bilkei-Gorzo et al., 2008
	PDyn −/−	N/A	Increased Time in Lit Area		Mice, C57Bl/6	Wittmann et al., 2009
Conditioned Fear	NorBNI, JDTic (IP)	6d before training; 8d before testing	Decreased Conditioned Fear		Rats, CD	Knoll et al., 2007
Stress-Induced Place Aversion	NorBNI	1h before stress	Blocked CPA		Mice, C57Bl/6	Land et al., 2008
	PDyn −/−	N/A
BETWEEN STRESSORS
Forced Swim	ANTI (IP)	1, 19, 23h after	Decreased Immobility		Rats, CD	Mague et al., 2003
	NorBNI, JDTic (SC)	After				Beardsley et al., 2005
Learned Helplessness	NorBNI (ICV, NAc, HIP)	1d after training, 3d before testing	Decreased Escape Failures (ICV, NAc)		Rats, CD	Newton et al., 2000
	NorBNI (NAc, HIP)		Decreased Escape Failures (NAc, HIP)		Rats, CD	Shirayama et al., 2004
AFTER STRESSORS
Stress-Induced Deficit in Novel Object Recognition	NorBNI (IP)	Immediately after 2nd swim session	Decreased Deficit in NOR		Mice, C57Bl/6	Carey et al., 2009

NorBNI, GNTI and JDTic, KOR Antagonists; PDyn −/−, prodynorphin knockout mice; KOR −/−, kappa opioid receptor knockout mice; NAc, nucleus accumbens; HIP, hippocampus; ICV, intracerebroventricular; IP, intraperitoneal; IC, intracisternal; CD, Sprague-Dawley; CPA, conditioned place aversion; NOR, novel object recognition;

^*, swim session parameters differed from those typically used to study KOR antagonists, see text for details.