Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of cyclic GMP, glutamate, and GABA.
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 micromol/L), S-nitroso-N-acetylpenicillamine (SNAP; 200 micromol/L), or 3-morpholinosydnonimine (SIN-1; 200 micromol/L) enhanced the acetylcholine release rate. The guanylyl cyclase inhibitor 1H-(1,2,4)-oxodiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L) abolished the effects of DEANO and SIN-1. 6-(Phenylamino)-5,8-quinolinedione (LY-83583; 100 micromol/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 micromol/L 6,6-dinitroquinoxaline-2,3-dione (DNQX) and 10 micromol/L (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Simultaneous superfusion with 50 micromol/L quinpirole and 10 micromol/L 7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83566) was ineffective. Superfusion with 500 micromol/L DEANO decreased the release of acetylcholine. The inhibitory effect of 500 micromol/L DEANO was reversed to an enhanced release on superfusion with 20 micromol/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.
Prast
H
H
Department of Pharmacology and Toxicology, University of Innsbruck, Austria.
Tran
M H
MH
Fischer
H
H
Philippu
A
A
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000109:Acetylcholine / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000378:metabolism*; D004048:Diethylamines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides; D009714:Nucleus Accumbens / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000502:physiology; D011954:Receptors, Dopamine / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000109:Acetylcholine; D006152:Cyclic GMP; D004048:Diethylamines; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D006162:Guanylate Cyclase; D009569:Nitric Oxide; D009589:Nitrogen Oxides; D011810:Quinoxalines; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; C087229:diethylamine dinitric oxide adduct; C044846:SKF83566