Table 1.

Behavioral observations following pharmacological interventions or genetic manipulations of the NPY system.

Rodent Models	Pharmacological Intervention or Genetic Manipulation	Route of Administration/ Region	Direction of Behavioral Effect	Reference
Anxiety-like Behavior	NPY	i.c.v. BLA, CeA Hippocampus Lateral Septum LC	Decrease	[67–70] [73–75] [71, 72] [77] [76]
	NPY knockout		Increase	[65]
	Y1R agonists	i.c.v. CeA Hippocampus	Decrease	[69, 86] [75, 88] [87]
	Y1R antagonists	i.c.v. PAG LC Hypothalamus CeA	Increase No effect	[89–91] [89]
	Y1R knockout		Increase	[83–85]
	Y2R agonist	i.c.v. LC Lateral septum BLA (high dose)	No effect Decrease	[67–69, 86] [76] [94] [96]
	Y2R antagonists	CeA	Decrease	[98]
	Y2R knockout	Global, BLA or CeA GABAergic neurons in CeA	Decrease Increase	[99–103] [97]
	Y4R knockout		Decrease	[100, 102]
	Y5R agonist	i.c.v.	Decrease	[86]
	Y5R antagonist	BLA	Decrease	[105]
Arousal	NPY	i.c.v., BLA CeA	Decrease No effect	[67, 92, 110] [110]
	NPY knockout		Increase	[66]
	Y1R agonists	i.c.v.	Decrease	[67]
	Y2R	i.c.v.	No effect	[67]
	Y2R knockout		Increase	[66]
Fear	NPY	i.c.v., Amygdala	Decrease	[110, 116–118]
	NPY knockout		Increase	[119]
	Y1R agonists	i.c.v.	Decrease	[116]
	Y1R antagonists	i.c.v. Amygdala	Block NPY effects Increase	[116] [110]
	Y1R knockout		Increase	[117]
	Y2R knockout		No effect	[119]
Depression-like Behavior	NPY	i.c.v., Hippocampus	Decrease	[122–125]
	Y1R agonists	i.c.v.	Decrease	[124]
	Y1R antagonists	i.c.v.	Block NPY effects	[124]
	Y1R knockout		Increase	[81]
	Y2R antagonists	i.c.v.	Decrease	[124]
	Y2R knockout		Decrease	[101]
	Y4R knockout		Decrease	[100, 102]
Depression Models (OBX or FSL)	NPY		Decrease (OBX)	[139]
	Y1R agonist	i.c.v.	Decrease (OBX)	[139]
	Y2R agonist	i.c.v.	Increase (OBX)	[141]
	Y2R antagonist	i.c.v.	Decrease (OBX)	[140]
	Y5R antagonist	i.c.v.	Decrease (FSL)	[134]
PTSD models (PSS and SPS)	NPY	Intranasal, Hippocampus	Decrease anxiety, arousal, fear, depression-like behaviors	[147, 149, 151]
	Y1R antagonist	Hippocampus	Increase anxiety, arousal	[147]