Table 2.

Neurochemical evidence supporting a negative impact of N/OFQ in stress, anxiety, and mood

Preparation	Findings	Reference
Rat dorsal raphe slice	N/OFQ increases in K+-driven rectifying current	Vaughn and Chrisie, 1996
Rat cortical synaptosomes	N/OFQ decrease of 5-HT and NE release	Siniscalchi et al., 1999; Marti et al., 2003; Mela et al., 2004
Rat neocortical slice	N/OFQ decrease of NE release	Okawa et al., 2001; Siniscalchi et al., 2002
Rat locus coeruleus in vivo	N/OFQ decrease of NE release	Okawa et al., 2001
CORT and ACTH levels after N/OFQ (icv)	Increases in plasma levels under mild stress conditions	Devine et al., 2001, 2003; Nicholson et al., 2002; Fernandez et al., 2004; Leggett et al., 2006
Acute restaint stress in rats	Decreases in NOC/OFC that are replenished in 24 hrs	Devine et al., 2003
N/OFQ (icv)	Increased brain experession of CRF and POMC	Leggett et al., 2006
Corticosterone levels after central N/OFQ	Cort levels increased after dosing in lateral ventricle and BNST but not amygdala	Green et al., 2007
N/OFQ into dorsal raphe nucleus of rats	Deccreasd 5-HT release and efflux that is prevented by an antagonist	Tao et al., 2007
Rat brain synaptosomes and slices	N/OFQ down-regulation of DA function	Olianas et al., 2008
Acute and repeat defeat stress	Prepro-N/OFQ and receptor mRNA increased in limbic structures	Green and Devine, 2009
Forced-Swim	decreased 5-HT outflow from DR neurons that is exacerbated by N/OFQ	Nazzaro et al., 2009
Restraint Stress - rat	Increased expression of N/OFQ in hippocampal CA1, CA3 and the dentate gyrus; increased plasam corticosterone	Nativio et al., 2012

ACTH: adrenocorticotropic hormone

BNST: bed nucleus of stria terminalis

DA: dopamine

HPA: hypothalamic-pituitary axis

5-HT: 5-hydroxytryptamine or serotonin

Icv: intracerebroventricular

NE: norepinephrine