Caffeine-induced potentiation of GABA effects on frog spinal cord: an electrophysiological study

A parasagittal slice of the frog spinal cord was kept in vitro for electrophysiological recordings from dorsal and ventral roots. Low concentrations of caffeine (50 microM) which had relatively small effects on baseline electrical activity, increased the depolarizing action of GABA on dorsal root fibres by 50%. A similar result was also obtained when GABA motoneuronal responses were tested. On dorsal roots the potentiation of GABA responses by caffeine was reflected by a significant decrease in GABA ED50 value without change in the maximal response amplitude; this enhancing action of caffeine was not blocked by bicuculline (5 microM) but was abolished by flurazepam (5 microM) or by Ca2+ antagonists (Mn2+ and Cd2+). Blockade of interneuronal activity by procaine left the potentiating action of caffeine unchanged. High doses of caffeine (up to 1 mM) produced a seemingly non-competitive antagonism of GABA responses. We suggest that caffeine can modulate GABA responses through two different mechanisms: a potentiation of GABA effects (seen with low doses of caffeine) probably due to Ca2+ mobilization and an antagonism of GABA responses (typically seen with large doses of caffeine) perhaps caused by block of GABA receptor-activated channels. This novel caffeine-GABA interaction may be useful to interpret some of the effects of caffeine on mammalian behaviour.