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Nitric Oxide‐Induced Release of Acetylcholine in the Nucleus Accumbens: Role of Cyclic GMP, Glutamate, and GABA
Author(s) -
Prast H.,
Tran M. H.,
Fischer H.,
Philippu A.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71010266.x
Subject(s) - nucleus accumbens , acetylcholine , glutamate receptor , chemistry , cyclic gmp , nitric oxide , neuroscience , biophysics , pharmacology , biochemistry , biology , organic chemistry , receptor
We have previously shown that the basal acetylcholine release in the ventral striatum is under the enhancing influence of endogenous nitric oxide (NO) and that NO donors cause pronounced increases in the acetylcholine release rate. To investigate the role of cyclic GMP, glutamate, and GABA in the NO‐induced acetylcholine release, we superfused the nucleus accumbens, (Nac) of the anesthetized rat with various compounds through a push‐pull cannula and determined the neurotransmitter released in the perfusate. Superfusion of the Nac with the NO donors diethylamine/NO (DEANO; 100 µmol/L), S ‐nitroso‐ N ‐acetylpenicillamine (SNAP; 200 µmol/L), or 3‐morpholinosydnonimine (SIN‐1; 200 µmol/L) enhanced the acetylcholine release rate. The guanylyl cyclase inhibitor 1 H ‐(1,2,4)‐oxodiazolo(4,3‐ a )quinoxalin‐1‐one (ODQ; 10 µmol/L) abolished the effects of DEANO and SIN‐1. 6‐(Phenylamino)‐5,8‐quinolinedione (LY‐83583; 100 µmol/L), which also inhibits cyclic GMP synthesis, inhibited the releasing effects of DEANO and of SNAP, whereas the effect of SIN‐1 on acetylcholine release was not influenced. The DEANO‐induced release of acetylcholine was also abolished in the presence of 20 µmol/L 6,6‐dinitroquinoxaline‐2,3‐dione (DNQX) and 10 µmol/L (±)‐2‐amino‐5‐phosphonopentanoic acid (AP‐5). Simultaneous superfusion with 50 µmol/L quinpirole and 10 µmol/L 7‐bromo‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1 H ‐3‐benzazepine (SKF 83566) was ineffective. Superfusion with 500 µmol/L DEANO decreased the release of acetylcholine. The inhibitory effect of 500 µmol/L DEANO was reversed to an enhanced release on superfusion with 20 µmol/L bicuculline. Bicuculline also enhanced the basal release rate. These findings indicate that cyclic GMP mediates the NO‐induced release of acetylcholine by enhancing the outflow of glutamate. Dopamine is not involved in this process. Only high concentrations of NO increase the output of GABA, which in turn decreases acetylcholine release. Our results suggest that cells that are able to release glutamate, such as glutamatergic neurons, are the main target of NO in the Nac.