Rainer K. Reinscheid

University of California Irvine, USA

Abstract

[O09] Pharmacology and genetics of the Neuropeptide S system

Neuropeptide S (NPS) has been shown to promote arousal and wakefulness, produce anxiolytic-like effects and facilitate fear extinction in rodents. In addition, NPS was found to reinstate drug-seeking behavior and attenuate neurochemical effects and psychotic-like behavioral changes produced by NMDA-receptor antagonists. Its effects on anxiety behaviors and fear memories appear to be mediated by NPS receptors in the amygdala where it modulates glutamatergic neurotransmission. While all these recent findings were made in preclinical animal models, much less is known about the physiological functions of the NPS system in humans.

A coding polymorphism in the human NPS receptor (NPSR) gene was discovered to occur with high frequency in the human gene pool. The single nucleotide polymorphism encodes an Asn to Ile exchange at position 107 of the receptor protein. The two variants of human NPSR differ substantially in their sensitivity to the natural agonist, with NPSR Ile107 being 5-10 fold more sensitive to NPS than NPSR Asn107. It is reasonable to assume that such a significant difference in agonist efficacy might produce phenotypical consequences. Indeed, two recent genetic association studies found evidence that NPSR genotypes might be associated with normal human behavior or psychiatric illness. First, we have recently found evidence that the homozygous NPSR Asn107 genotype is underrepresented in male panic disorder patients. The second study identified linkage of NPSR genotypes with average bedtime behavior in a normal population cohort where each copy of the more sensitive NPSR Ile107 variant delays bedtime by 15 minutes. These results indicate that the NPS system may be involved in modulation of anxiety as well as arousal states in humans.

Keywords: arousal, anxiety, polymorphism, genetic

Biography

Rainer K. Reinscheid obtained his Ph.D. in neurobiology from the University of Hamburg, Germany, working on neuropeptides in invertebrates. During his postdoc at Hoffmann-La Roche, Switzerland, he isolated Orphanin FQ (also known as nociceptin) as the natural ligand of an orphan GPCR. His research has focused on elucidation of physiological functions of orphan GPCRs by using pharmacological, neuroanatomical and genetic approaches. Recently, he started to explore a novel peptide transmitter in the brain, called Neuropeptide S.

Rainer K. Reinscheid is an Associate Professor at the University of California, Irvine, in the Department of Pharmaceutical Sciences.