3,4-DIAMINOPYRIDINE AND CHOLINE INCREASE IN-VIVO ACETYLCHOLINE-RELEASE IN RAT STRIATUM

We investigated the effects of choline, 3,4-diaminopyridine and their combination on acetylcholine release from the corpus striatum of freel y moving rats which were treated or not with atropine. Intraperitoneal administration of choline or intrastriatal administration of 3,4-diam inopyridine increased acetylcholine levels in striatal dialysates in a dose-dependent manner. When 3,4-diaminopyridine treatment was combine d with choline, the observed effect was considerably greater than the sum of the increases produced by choline or 3,4-diaminopyridine alone. Administration of atropine (1 mu M) in the dialysing medium was also found to be effective to stimulate striatal acetylcholine levels. 3,4- Diaminopyridine did not affect acetylcholine levels under these condit ions. Whereas the choline-induced increase in acetylcholine release wa s significantly potentiated by atropine, co-administration of 3,4-diam inopyridine with choline failed to produce a further significant incre ase in the presence of atropine. These results suggest that a highly e ffective means for increasing acetylcholine release involves two concu rrent treatments that increase neuronal choline levels and inhibition of the negative feedback modulation of acetylcholine release.