NITRIC-OXIDE MODULATES THE RELEASE OF ACETYLCHOLINE IN THE VENTRAL STRIATUM OF THE FREELY MOVING RAT

The influence of nitric oxide on acetylcholine release in the ventral striatum was investigated by the push-pull superfusion technique in th e conscious, freely moving rat. Superfusion with the nitric oxide dono rs S-nitroso-N-acetylpenicillamine or with 3-morpholino-sydnonimine ca used a pronounced increase in striatal acetylcholine release. This eff ect was prevented by superfusion with tetrodotoxin. Pre-superfusion wi th the guanylyl cyclase inhibitor methylene blue abolished the effect of 3-morpholino-sydnonimine. Superfusion of the ventral striatum with the guanylyl cyclase inhibitor LY83583 decreased acetylcholine release by 60% of basal release, whereas the less specific guanylyl cyclase i nhibitor methylene blue was ineffective in this respect. Superfusion o f the ventral striatum with inhibitors of nitric oxide synthase also l ed to different effects on basal acetylcholine release. Superfusion wi th L-N-G-methylarginine did not influence basal acetylcholine release, whereas superfusion with L-N-G-nitroarginine or with L-N-G-nitroargin ine methyl ester led to a substantial decrease in acetylcholine output , the latter compound being more effective. The effect of L-N-G-nitroa rginine was abolished by simultaneous superfusion with L-arninine. The effects of NO donors and of LY83583 suggest that NO increases acetylc holine release, probably by a cGMP-dependent mechanism. The effectiven ess of nitric oxide synthase inhibitors shows that the activity of str iatal neurons is under the permanent influence of nitric oxide, that l eads, via a direct or indirect mechanism, to continuous enhancement of acetylcholine release. In conclusion, our findings suggest that NO sy nthesized in the ventral striatum acts as an intercellular messenger w hich modulates acetylcholine release.