Nitric oxide-mediated anxiolytic-like and antidepressant-like effects in animal models of anxiety and depression.
The effects of microinjection of the nitric oxide (NO) precursor l-arginine (l-Arg), the NO synthase (NOS) inhibitors N-methyl-l-arginine (l-NAME) and 7-nitroindazole (7-NI), and the cyclic guanosine 3',5'-monophosphate (cGMP) analog 8-Br-cGMP into the dorsal raphe nucleus (DRN) were assessed in rats using the elevated plus maze (EPM) and the forced swim test (FST). l-Arg (100 and 200 nmol) produced an anxiolytic-like effect in the EPM. 8-Br-cGMP (25 and 50 nmol) dose-dependently increased locomotor activity. In the FST, antidepressant-like effects were produced by l-Arg (50 and 100 nmol) and 8-Br-cGMP (12.5 and 25 nmol). Dual effects were observed with NOS inhibitors l-NAME and 7-NI in both the EPM and FST. While low doses of l-NAME (25 nmol) or 7-NI (1 nmol) induced a selective increase in EPM open arm exploration and a decrease in immobility time in the FST, high doses (l-NAME 400 nmol, 7-NI 10 nmol) decreased locomotor activity. These results show that interference with NO-mediated neurotransmission in the DRN induced significant and complex motor and emotional effects. Further studies are needed to elucidate the mechanisms involved in these effects.
Spiacci
A
A
State University of Maringá, Department of Pharmacology, Maringá, Brazil.
Kanamaru
F
F
Guimarães
F S
FS
Oliveira
R M W
RM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000503:physiopathology* / Q000523:psychology*; D001120:Arginine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003863:Depression / Q000503:physiopathology* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; D001120:Arginine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester