title: Caffeine impairs the acquisition and retention, but not the consolidation of Pavlovian conditioned freezing in mice.
abstract: BACKGROUND
  The psychoactive substance, caffeine, may improve cognitive performance, but its direct impact on learning and memory remains ill defined. Conflicting reports suggest that caffeine may impair as well as enhance Pavlovian fear conditioning in animals and its effect may vary across different phases of learning.
  
  
  OBJECTIVE
  The purpose of this study is to dissect the effect of a motor-stimulant dose of caffeine (30 mg/kg intraperitoneal (i.p.)) on acquisition, retrieval or consolidation of conditioned fear in C57BL/6 mice.
  
  
  METHODS
  Fear conditioning was evaluated in a conditioned freezing paradigm comprising 3 tone-shock pairings and a two-way active avoidance paradigm lasting two consecutive days with 80 conditioning trials per test session.
  
  
  RESULTS
  Conditioning to both the discrete tone-conditioned stimulus (CS) and the context was markedly impaired by caffeine. The deficits were similarly evident when caffeine was administered prior to acquisition or retrieval (48 and 72 h after conditioning); and the most severe impairment was seen in animals given caffeine before acquisition and before retrieval. A comparable deficit was observed in the conditioned active avoidance test. By contrast, caffeine administered immediately following acquisition neither affected the expression of tone freezing nor context freezing.
  
  
  CONCLUSIONS
  The present study challenges the previous report that caffeine primarily disrupts hippocampus-dependent conditioning to the context. At the relevant dose range, acute caffeine likely exerts more widespread impacts beyond the hippocampus, including the amygdala and striatum that are anatomically connected to the hippocampus; together, they support the acquisition and retention of fear memories to discrete stimuli as well as diffused contextual cues.
authors.affiliation: Legacy Research Institute, 1225 NE Second Avenue, Portland, OR, 97232, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Dubroqua
authors.forename: Samuel R L
authors.initials: SR
authors.lastname: Low
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Yee
authors.forename: Philipp
authors.initials: P
authors.lastname: Singer
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D005239:Fear / Q000187:drug effects; D005615:Freezing; D006624:Hippocampus / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012153:Retention, Psychology / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine