Neuropeptide S

Justin P. Smith

What are they?

• Small protein-like molecules (peptides)• Used by neurons to communicate• Influence activity, act on neuronal surface

receptors• NPSR- G-protein coupled receptor– Stimulates Ca++ and cAMP

NPS Structure

Discovered via reverse pharmacology, deorphanized receptor

NPS functional role in:

• Anxiety• Arousal• Locomotion • Food intake• Memory• Drug addiction

NPS expression• Co-expressed with excitatory

neurotransmitters• Additional (+) input to postsynaptic target of

excitatory neurons• Anxiolytic-like effects– EPM, light-dark box, open field, elevated zero

maze– No effect in: Tail suspension or forced swim

NPSR

• NPSR mRNA- expressed in stress related areas– Amygdala– BNST– Hypothalamus– Raphe Nucleus– Ventral tegmental area

• Pre-synaptic inhibitory effects of NPS on 5-HT and NE in cortex, role in anxiolytic effect?

NPS & Learning and Memory

• Regulation of learning process– Interferes with contextual expression of fear

memory (but not auditory)– Facilitates conditioned fear response extinction

(when injected into amygdala)

• Improved memory– Novel object recognition test– Morris water maze

When finding articles

• Neuroscience and behavior• Use this review as a starting point– Check to see what the groups mentioned herein

are doing now– Key words extravaganza – Pick what interests you!– Ask me or Dr. Summers for help