Neuropeptide S stimulates dopaminergic neurotransmission in the medial prefrontal cortex

Abstract

Neuropeptide S (NPS) is known to produce anxiolytic-like effects and facilitate extinction of conditioned fear. Catecholaminergic neurotransmission in the medial prefrontal cortex (mPFC) has been suggested to be crucially involved in these brain functions. In the current study, we investigated the effect of NPS on the release of dopamine and serotonin in the mPFC by in vivo microdialysis in rats. Central administration of NPS dose-dependently enhanced extracellular levels of dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid, with maximal effects lasting up to 120 min. In contrast, no effect on serotonergic neurotransmission was detected. Dopamine release in the mPFC has been previously linked to modulation of anxiety states and fear extinction. The present results may thus provide a physiological and anatomical basis for the reported effects of NPS on these behaviors.

Fig. 1

Dose-dependent effects of i.c.v. NPS on extracellular levels of dopamine in the mPFC. NPS significantly increased extracellular dopamine levels. (a) Time course of extracellular dopamine levels following central administration of saline or increasing doses of NPS. Dopamine levels were normalized to the average of four baseline samples. * p < 0.05, ** p < 0.01, *** p < 0.001, 1 nmol NPS versus saline; # p < 0.05, ## p < 0.01, ### p < 0.001, 10 nmol NPS versus saline; Bonferroni post-hoc test after significant treatment effect in two-way ANOVA. (b) Cumulative dopamine levels between 0 and 120 min post injection, calculated as area under the curve (AUC), ** p < 0.01, *** p < 0.001 versus saline; Dunnett’s post-hoc test after significant one-way ANOVA.

Fig. 2

Central administration of 1 nmol NPS significantly increased extracellular levels of DOPAC in the mPFC. (a) Time course of extracellular DOPAC as a percentage of basal levels. * p < 0.05 versus saline, t-test after significant treatment effect in two-way ANOVA. (b) Cumulative DOPAC levels between 0 and 120 min post injection, calculated as area under the curve (AUC), * p < 0.05 versus saline, t-test.

Fig. 3

NPS administration had no significant effects on extracellular levels of 5-HT. (a) 5-HT percentage of basal levels in the mPFC after saline or NPS i.c.v. administration. (b) Cumulative 5-HT levels between 0 and 120 min post injection, calculated as area under the curve (AUC).

Fig. 4

NPS administration had no effect on extracellular levels of 5-HIAA. (a) 5-HIAA percentage of basal levels in the mPFC after saline or NPS i.c.v. administration. (b) Cumulative 5-HIAA levels between 0 and 120 min post injection, calculated as area under the curve (AUC).