Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1 mg/mL drinking solution for 30 days) on short- and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats. Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels. In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age. These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding.

This article is part of a Special Issue entitled ‘Cognitive Enhancers’.