Table 2.

Evidence that KOR activation contributes to stress-induced reinstatement of opioid seeking behavior in preclinical models

KOR ligand	Species	Sex	Drug of abuse/protocol	Stressor/pain	Main outcome	Reference	Pain component
Nor-BNI	Sprague Dawley rats	Male	Heroin IVSA and stress-induced reinstatement	Yohimbine (YOH)	KOR blockade reduced reinstatement	(Zhou et al. 2013)	No
Nor-BNI	Sprague Dawley rats	Male	Heroin IVSA and stress-induced reinstatement	Food deprivation	KOR blockade reduced reinstatement	(Sedki et al. 2015)	No
Nor-BNI	Mouse (C57B1/6)	Male	Morphine CPP and drug-prime reinstatement	Incisional postsurgical pain model	KOR blockade enhanced drug-primed reinstatement	(Nwaneshiudu et al. 2020)	Yes
LY2456302	Sprague Dawley rats	Male	Oxycodone IVSA and cue-induced reinstatement	None	KOR blockade had no effect on reinstatement	(Bossert et al. 2019)	No
CJ-15208 (Cyclo[Pro-Sar-Phe-D-Phe]) or Nor-BNI	Mouse (C57B1/6)	Male	Morphine CPP and stress-induced reinstatement	Forced swim stress	Both drug interventions prevented reinstatement	(Brice-Tutt et al. 2020; Ferracane et al. 2020)	No
Buprenorphine + naltrexone	Sprague Dawley rats	Male	Morphine CPP and drug-prime reinstatement	None	The combination blocked drug-primed reinstatement	(Cordery et al. 2014)	No
Dezocine (partial MOR agonist, KOR antagonist) or buprenorphine	Sprague Dawley rats	Male	Morphine CPP and drug-prime reinstatement	None	Both drug interventions prevented reinstatement	(Wu et al. 2019)	No
Nor-BNI	Sprague Dawley rats	Male	Morphine CPP and drug-prime reinstatement	None	KOR blockade did not alter drug-primed reinstatement	(He et al. 2019)	No