Temperature-dependent modulation of excitatory transmission in hippocampalslices is mediated by extracellular adenosine

Although extracellular adenosine concentrations in brain are increased mark edly by a variety of stimuli such as hypoxia and ischemia, it has been diff icult to demonstrate large increases in adenosine with stimuli that do not result in pathological tissue damage. The present studies demonstrate that increasing the temperature at which rat hippocampal brain slices are mainta ined (typically from 32.5 to 38.5 degrees C) markedly inhibits excitatory s ynaptic transmission. This effect was reversible on cooling, readily repeat able, and was blacked by A(1) receptor antagonists and by adenosine deamina se, suggesting that it was mediated by increased activation of presynaptic adenosine A(1) receptors by endogenous adenosine, This increase in adenosin ergic Inhibition was not a response to hyperthermia per se, because it coul d be elicited by temperatures that remained entirely within the hypothermic range (e.g., from 32.5 to 35.5 degrees C). The increased activity at A(1) receptors appeared to be attributable to the direct release of adenosine vi a nucleoside transporters; the release of adenine nucleotides, linked to ei ther the activation of NMDA receptors or the increased efflux of cAMP, appe ared not to be involved. These results suggest that changes in brain temper ature can alter the regulation of extracellular adenosine in rat brain slic es and that increased adenosine release may be an important regulatory mech anism for countering increased excitability consequent to increased brain t emperature.