DOSE- AND TASK-DEPENDENT EFFECTS OF NEUROPEPTIDE S ON IMPULSIVITY, ATTENTION, AND CONSUMMATORY BEHAVIOR IN RATS

Neuropeptide S (NPS) is a neurotransmitter with both anxiolytic and pro-arousal properties. A genetic variant of the NPS receptor has been associated with maladaptive impulsivity; however, its functional role in impulsive behavior has not yet been evaluated. Here, we examined the effects of intracerebroventricular (i.c.v.) NPS
(0, 0.1, 1.0, or 2.0 nmol) on impulsivity and attention using the Go/NoGo and two- choice serial reaction time task (2-CSRT), respectively, and on sucrose self- administration to assess consummatory behavior in male and female Wistar rats. In the Go/NoGo task, rats were required to withhold lever pressing during NoGo cues and respond during Go cues to obtain sucrose. Intermediate and high NPS doses reduced premature responses during NoGo cues, whereas the highest dose also reduced Go responses. In the 2-CSRT, the rewarded lever switched randomly between left and right, and attention was indexed by correct responses; 2.0 nmol NPS impaired performance. Finally, intermediate and high NPS doses reduced sucrose self-administration. These findings indicate that NPS produces dose- and task-dependent effects. Specifically, 1.0 nmol showed an anti-impulsive profile (reduced NoGo premature responses without affecting Go responding), whereas 2.0 nmol combined anti- impulsive and anti-consummatory effects (reduced NoGo and Go responding). In sucrose self-administration tasks, NPS showed anti-consummatory effects, and the decreased performance in the 2-CSRT was interpreted as secondary to these effects.
Overall, NPS may represent a potential target for anti-impulsive therapies.
Study supported by Italian Ministry of University and Research PRIN-PNRR
P2022E4MLS and NIH/NIAAA 1R01AA030888-01A1 to N.C.