Changes in hippocampal adenosine efflux, ATP levels, and synaptic transmission induced by increased temperature

Previous studies have demonstrated that when the temperature of hippocampal brain slices is increased, there is a corresponding depression of synaptic potentials mediated by an increased activation of presynaptic adenosine A, receptors. The present experiments demonstrate that when the temperature o f hippocampal slices is raised from 32.5 degreesC to either 38.5 degreesC o r 40.0 degreesC there is a marked, temperature-dependent increase in the ef flux of endogenous adenosine and a corresponding decrease in excitatory syn aptic responses. The increase in efflux is rapidly reversible on lowering t he slice temperature and the temperature-induced efflux is repeatable. Cont rol experiments suggest that this increased efflux of adenosine is not the result of hypoxia or ischemia secondary to a temperature-induced increase i n the metabolic rate of the slice. The increase in adenosine efflux was not accompanied by any significant change in the ATP levels in the brain slice , whereas a hypoxic stimulus sufficient to produce a comparable depression of excitatory transmission produced an similar to 75% decrease in ATP level s. These experiments indicate that changes in brain slice temperature can a lter purine metabolism in such a way as to increase the adenosine concentra tion in the extracellular space, as well as adenosine efflux from hippocamp al slices, in the absence of significant changes in ATP levels. Synapse 41: 58-64, 2001. (C) 2001 Wiley-Liss, Inc.