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NPS and Caffeine

NPS and Caffeine. A Sordid Tale of Antagonism. 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.

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NPS and Caffeine

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  1. 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

  7. 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: 726-730

  8. 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

  9. Modification of Caffeine Effects on the Affect-Modulated Startle by Neuropeptide S Receptor Gene Variation Domschke et al. (2012) Psychopharmacology 222: 533-541

  10. 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)

  11. Fin.

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