Recent studies demonstrated potent behavioral effects of centrally applied neuropeptide S (NPS) in mice and rats. These include increased arousal and wakefulness, facilitation of fear extinction and object memory consolidation and anxiolysis. Here, we compared the effects of NPS on both social and nonsocial memory, in male rats, and on social preference/social anxiety versus non-social anxiety after either intracerebroventricular (icv) or nasal application. Intranasal application of neuropeptides has been successfully employed to alter behavioral parameters in humans and rodents, but studies concerning nasal application of NPS are lacking so far.
First, we confirmed the facilitatory effect of icv NPS (1 nmol) on object discrimination after an inter-exposure interval (IEI) of 240 min. These effects were context dependent, as icv NPS (1 nmol) did not prolong social memory in a social discrimination paradigm.
Second, we confirmed the anxiolytic effect of icv NPS (1 nmol) on the elevated plus-maze, whereas neither icv NPS (1 nmol) nor NPS receptor antagonist (10 nmol) altered social preference/social avoidance behavior. Third, nasal NPS (4e40 nmol applied topically on the rhinarium) facilitated object discrimination in a dose-dependent manner. Also, the anxiolytic effect of NPS on the elevated plus-maze could be confirmed after nasal administration (40 nmol). In contrast, identical doses of subcutaneously injected NPS failed to produce corresponding behavioral effects in both tests.
Our findings provide evidence for memory-enhancing and anxiolytic effects of icv NPS in a non-social context. We could further show that these effects are context-specific, as social memory and social preference behavior remained unchanged after icv NPS. The effects of icv NPS were replicated by nasal application of the neuropeptide. Thus, nasal application of NPS seems to be a useful method in rodents for screening for behavioral or physiological effects before more specific and time-consuming, intracerebral methods are employed, and may represent a viable therapeutic approach for NPS treatment ofpatients with psychiatric illnesses such as anxiety or panic disorders.