1. A Sordid Tale of Antagonism
NPS and Caffeine
A Sordid Tale of Antagonism

2. Caffeine
“Caffeine is the most commonly used stimulant to combat inappropriately timed sleepiness.”
Extends sleep latency
Decreases total sleep time
Increases sleep fragmentation
In rats, leads to reduced food intake leading to weight loss

3. Proposed Mechanisms
Antagonist of the dopamine-adenosine interaction via adenosine A2A receptors (Gs cAMP) in striatum
Antagonism of the adenosine A1 receptor (Gi/o cAMP) of the basal forebrain neurons

4. Neuropeptide S 20 Amino Acid Neuropeptide
Binds NPS-R (G-Protein coupled receptor)
Expressed located almost solely in the brain stem region close to the locus coeruleus and Barrington’s nucleus
Other areas of weak expression exist (dorsomedial nucleus of the hypothalamus and amygdala)
Sleep-wake cycle
Arousal
Locomotor activity
Feeding

5. Caffeine Treatment Regulates Neuropeptide S System Expression in the Rat Brain
Lage et al. (2006) Neuroscience Letters 410: 47-51

6. The Experiment Adulte male Sprague-Dawley rats 12H Light-Dark
Doesn’t identify experimental timeframe
Studied the effects of acute and chronic caffeine treatment

10. Role of the Ecto-Nucleotideases in the Cooperative Effect of Adenosine and Neuropeptide-S on Locomotor Activity in Mice
Pacheco et al. (2011) Pharmacology, Biochemistry and Behavior 99:

11. The Experiment Male albino CF-1 mice 12H Light-Dark
Experiments done in the light cycle >=[
Investigated whether the involvement of adenosine in the hyperlocomotor effect of NPS is due to its production via ecto- nucleotidases pathway
Pre-treated mice with AOPCP (α,β-mehtylene-adenosine 5’- diphosphate), an ecto-5’-nucleotidase inhibitor
NPS challenge
Investigated whether NPS treatment is able to modify the E- NTPDase and ecto-5’-nucleotidase activities in hippocampal and striatal mouse brain slices

14. Modification of Caffeine Effects on the Affect-Modulated Startle by Neuropeptide S Receptor Gene Variation
Domschke et al. (2012) Psychopharmacology 222:

15. The Experiment 124 unrelated, healthy individuals
AA/AT/TT polymorphisms were determined
One-session, double-blind placebo controlled between- subject designed Caffeine challenge.
24 each of unpleasant, neutral, and pleasant pictures were shown to subjects (sequentially for 8s intervals)

17. Fin.