Glucose deprivation increases basal and electrically evoked transmitter release from rat striatal slices. Role of NMDA and adenosine A1 receptors.

We have investigated how glucose deprivation in vitro influences the basal and electrically evoked release of dopamine and acetylcholine from rat striatal slices and the role of endogenous activation of NMDA receptors and adenosine A1 receptors in determining the magnitude of this response. Rat striatal slices, preincubated with [3H]dopamine and [14C]choline, were superfused continuously and stimulated electrically. Before and during the second stimulation, some slices were superfused with glucose-free Krebs' solution. Such glucose deprivation caused a 2 to 3-fold increase of the electrically evoked, calcium-dependent release of endogenous adenosine (but not hypoxanthine and inosine) and [3H]dopamine and a 30% increase in release of [14C]acetylcholine. Glucose deprivation also caused a delayed increase in the release of [3H]dopamine, but not of [14C]acetylcholine. The dopamine release was not calcium dependent. The addition of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM), a selective adenosine A1 receptor antagonist, slightly enhanced the glucose deprivation-induced stimulatory effect on the evoked release of these two transmitters, whereas the NMDA receptor antagonist dizocilpine((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine; 3 microM) markedly attenuated the stimulatory effect of glucose deprivation. The change in basal dopamine release was not influenced by DPCPX, but was slightly attenuated by dizocilpine. In summary, the results suggest that lack of substrate induces release of both glutamate, which by actions on presynaptic NMDA receptors causes the release of dopamine, and of adenosine, which via adenosine A1 receptors reduces the electrically evoked release of both dopamine and acetylcholine.