POSTHYPOXIC RECOVERY OF ACETYLCHOLINE-RELEASE - DIFFERENT SENSITIVITYOF GUINEA-PIG NEOCORTICAL AND STRIATAL SLICES

The release of endogenous acetylcholine (ACh) was measured in superfus ed guinea-pig cortical and striatal slices, kept at rest or electrical ly stimulated at different frequencies, before and during severe hypox ic conditions as well as after reoxygenation. In the cortex the basal release was unchanged by 30-60 min of hypoxia while it was inhibited i n the striatum. The release evoked by short-term (2 min) stimulation a l 0.5 Hz was moderately reduced (to 76%) by 30 min hypoxia in the cort ex and in the striatum, but fully recovered after reoxygenation. The r elease evoked by continuous stimulation (from 5 to 10 to 20 Hz) was st rongly inhibited (to 12-30%) in both areas after 30 min of hypoxia. Af ter 30 min of reoxygenation, the recovery was complete in the cortex ( mainly provided with cholinergic axons), but it was incomplete in the striatum (rich in cholinergic interneurones). The extent of the recove ry in the latter area (i) was inversely related to stimulation frequen cy, (ii) did nor depend on the depletion of neurotransmitter stores, b ecause ACh tissue levels were fully restored by reoxygenation, and (ii i) was consistently facilitated by excitatory aminoacid antagonists, s lightly improved by the adenosine agonist R-phenylisopropyladenosine a nd unaffected by reducing the concentrations of radical species with c atalase and superoxide dismutase or N-omega-nitro-L-arginine. These re sults emphasize (i) the different vulnerability of the cortical and st riatal cholinergic structures, (ii) the high sensitivity of the striat al interneurones to the frequency of stimulation during the posthypoxi c recovery, and (iii) the relevant role played by endogenous glutamate on activity-dependent neurosecretory failure. Copyright (C) 1996 Else vier Science Ltd