Acute exposure to caffeine selectively disrupts context conditioning in rats

Rationale and objective: Acute caffeine administration has both beneficial and adverse effects on learning and memory; however, the brain regions underlying these effects remain unclear. Several experiments were conducted to examine the effects of acutely administered caffeine on the acquisition and expression of hippocampal-dependent and hippocampal-independent forms of conditioned fear. Methods: In the first experi- ment. caffeine (10, 20, or 30 mg/kg; IP) or vehicle was administered to rats 15 min prior to classical fear conditioning, which consisted of ten tone-shock pairings. Freezing to the conditioning context was measured 24 h later, whereas tone-elicited fear was measured 48 h later A second experiment examined possible state-dependent effects of caffeine by administering caffeine (30 mg/kg) or vehicle 15 min before conditioning and before testing. Results: Pretreatment of acute caffeine severely impaired the acquisition of context conditioning, a hippocampal dependent task. Tone conditioning, a hippocampal-independent task, was only modestly and non-significantly affected by caffeine (4-21% suppression compared with controls). The disruption of context conditioning was dose-dependent: 10 mg/kg had little effect on context or tone conditioning, whereas doses of 20 and 30 mg/kg caffeine severely disrupted context conditioning (73-87% suppression). In two subsequent experiments, it was found that caffeine's selective disruption of context conditioning could not be attributed to the fact that it is a weaker form of learning than tone conditioning or to state-dependent learning. Conclusions: Considered together, these results suggest that acute administration of caffeine may preferentially disrupt the acquisition of hippocampal-dependent learning, including context conditioning.