Opposite roles for neuropeptide S in the nucleus accumbens and bed nucleus of the stria terminalis in learned helplessness rats

• Infusion of NPS into the NAc shell produced antidepressant-like effects in LH rats.
• NPS antagonism by SHA68 in the BNST produced antidepressant-like effects.
• NPS in the NAc shell and SHA68 in the BNST did not alter memory or locomotion.
• The NPS system has a role in the NAc and BNST of LH rats in opposite directions.

The role of neuropeptide S (NPS) in depression remains unclear. We examined the antidepressant-like effects of NPS infusions into the shell or core regions of the nucleus accumbens (NAc) and into the bed nucleus of the stria terminalis (BNST) of learned helplessness (LH) rats (an animal model of depression). Infusions of NPS (10 pmol/side) into the NAc shell, but not the NAc core and BNST, exerted antidepressant-like effects in the LH paradigm. Implying that behavioral deficits could be improved in the conditioned avoidance test. Coinfusion of SHA68 (an NPS receptor antagonist, 100 pmol/side) with NPS into the NAc shell blocked these effects. In contrast, NPS receptor antagonism by SHA68 in the BNST induced antidepressant-like effects. Infusions of NPS into the NAc shell or SHA68 into the BNST did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. These results suggest that excitatory and inhibitory actions by the NPS system are integral to the depression in LH animals.