Table 1. Effects of nitric oxide-related drugs on defensive behavior when injected into the intradorsal periaqueductal gray region.
| Drug (dose) | Possible mechanism | Species | Animal model | Main effect | References |
|---|---|---|---|---|---|
| Carboxy-PTIO (0.3-3 nmol) | NO scavenger | Rat | VCT, EPM | Anxiolytic | 21,28*,33 |
| OA | No effect | ||||
| DEA/NO (150-600 nmol) | NO donor | Rat | OA | Pro-aversive | 35 |
| L-NOARG (10-100 nmol) | NOS inhibitor | Rat | EPM | Anxiolytic | 32* |
| L-NAME (100-200 nmol) | NOS inhibitor | Rat | EPM, T-maze | Anxiolytic | 31,32*,49 |
| OA | No effect | ||||
| Methylene blue (10-100 nmol) | sGC and NOS inhibitor | Rat | EPM | Anxiolytic | 50* |
| NOC-9 (75-150 nmol) | NO donor | Rat | OA | Pro-aversive | 34 |
| NPA (0.08-100 nmol) | Selective nNOS inhibitor | Rat, Mice | VCT, CET, RET | Anxiolytic | 33,36,51 |
| SIN-1 (150-300 nmol) | NO donor | Rat | OA | Pro-aversive | 28,34,35,45 |
| ODQ (0.3-3 nmol) | sGC inhibitor | Rat | EPM | Anxiolytic | 28*,31,52 |
| OA | No effect | ||||
| 7NI (40 nmol) | Preferential nNOS inhibitor | Rat | EPM | No effect | 52 |
Drugs: Carboxy-PTIO = 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt; DEA/NO = dieth-ylamine NONOate; L-NOARG = N(G)-nitro-L-arginine; L-NAME = N(G)-nitro-L-arginine methyl ester hydrochloride; NOC-9 = 6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine; NPA = n-propyl-L-arginine; SIN-1 = 3-(4-morpholinyl)syd-nonimine; ODQ = 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 7-NI = 7-nitro-indazol. Mechanisms: NO = nitric oxide; NOS = NO synthase; sGC = soluble guanylyl cyclase; nNOS = neuronal NOS. Models: VCT = Vogel conflict test; EPM = elevated plus-maze; OA = open arena; CET = cat exposure test; RET = rat exposure test. *Indicates a bell-shaped dose-response curve.