A POSSIBLE MECHANISM FOR THE AGLYCEMIA-INDUCED DEPRESSION OF GLUTAMATERGIC EXCITATION IN THE STRIATUM

We have studied the possible mechanisms underlying the decrease of exc itatory transmission induced by glucose deprivation by using electroph ysiological recordings in corticostriatal slices. Extracellular field potentials were recorded in the striatum after cortical stimulation; t hese potentials were progressively reduced by glucose deprivation. The reduction started 5 minutes after the onset of aglycemia. The field p otential was fully suppressed after 40 minutes of glucose deprivation. After the washout of the aglycemic solution only a partial recovery w as observed, Aglycemia also induced a delayed inward current during si ngle-microelectrode voltage-clamp recordings from spiny neurons. This inward current was coupled with an increased membrane conductance. The A1 adenosine receptor antagonists, 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 mu mol/L) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nm ol/L), significantly reduced the aglycemia-induced decrease of field p otential amplitude. Moreover, in the presence of CPT and CPX, a full r ecovery of the field potential amplitude after the interruption of the aglycemic solution was observed. Conversely, these antagonists affect ed neither the inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel b lockers glibenclamide (10 mu mol/L) and glipizide (100 nmol/L) had no effect on the aglycemia-induced decrease of the field potential amplit ude. We suggest that endogenous adenosine, but not ATP-dependent potas sium channels, plays a significant role in the aglycemia-induced depre ssion of excitatory transmission at corticostriatal synapses probably through a presynaptic mechanism. Moreover, adenosine is not involved i n the postsynaptic changes induced by glucose deprivation in spiny str iatal neurons.