title: Sensorimotor gating is disrupted by acute but not chronic systemic exposure to caffeine in mice.
abstract: BACKGROUND
  Caffeine is a psychostimulant drug that blocks adenosine A₁ and A₂A receptors (A₁Rs and A₂ARs). However, its ability to disrupt early sensory gating as indexed by prepulse inhibition (PPI), which is consistently disrupted by other psychostimulant agents, has never been convincingly demonstrated.
  
  
  OBJECTIVE
  To compare the impact of caffeine on PPI expression in C57BL/6 mice by two dose-response experiments differing in terms of chronicity, regimen, and route of administration. To study separately the acute effect of selective antagonists against A₁R or A₂AR.
  
  
  METHODS
  Caffeine (10, 30, 100 mg/kg, intraperitoneal (i.p.)) was either administered shortly before testing or via caffeinated drinking water (0.3, 1.0, 2 g/l) in home cages over 3 weeks. Two separate dose-response studies tested the acute effect of the selective A₁R antagonist, 1,3 dipropyl-8 cyclopentyl xanthine (DPCPX), and the selective A₂AR antagonist, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] (SCH 58261) (0.2, 1.0, 5.0 mg/kg, i.p.). The two drugs were combined in a final experiment to identify their potential synergistic interaction.
  
  
  RESULTS
  While the two lower acute doses of caffeine attenuated PPI, the highest dose potentiated PPI. By contrast, chronic caffeine exposure did not affect PPI. Neither DPCPX nor SCH 58261 altered PPI, and no synergism was observed when the two drugs were combined.
  
  
  CONCLUSIONS
  This is the first demonstration that acute caffeine disrupts PPI, but the relative contribution of A₁R and A₂AR blockade remains unclear, and possible non-adenosinergic mechanisms cannot be ruled out. The null effect under chronic caffeine exposure might involve the development of tolerance, but the precise receptor subtypes involved also warrant further investigation.
authors.affiliation: Laboratory of Behavioral Neuroscience, Legacy Research Institute, 1225 NE Second Avenue, Portland, OR, 97232, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Dubroqua
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Yee
authors.forename: Philipp
authors.initials: P
authors.lastname: Singer
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065808:Prepulse Inhibition / Q000187:drug effects*; D058915:Purinergic P1 Receptor Antagonists / Q000008:administration & dosage*; D011743:Pyrimidines / Q000494:pharmacology; D055139:Sensory Gating / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles; D014970:Xanthines; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine
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