Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in rats.
The effects of the NO donor molsidomine and the inhibitors of the NO synthase (NOS) 7-nitroindazole (7-NI) and NG-nitro-L-arginine methyl ester (L-NAME) on the motor hyperactivity induced by indirect (amphetamine and cocaine) or direct (SKF 38393 and bromocriptine) dopamine (DA) agonists were studied in rats. The hyperactivity induced by 0.5 mg/kg of amphetamine or 5 mg/kg of cocaine was potentiated in a dose-dependent manner by molsidomine (30-100 mg/kg), but attenuated by 7-NI (3-30 mg/kg) or L-NAME (3-30 mg/kg). The NOS inhibitors also inhibited the locomotor hyperactivity evoked by 15 mg/kg of SKF 38393 (a DA D1 agonist) or 5 mg/kg of bromocriptine (a DA D2 agonist). On the other hand, the hyperactivity induced by those direct DA receptor agonists was potentiated by molsidomine. The present findings provide further evidence for an interaction at the behavioral level between NO and the DA-mediated effects of amphetamine and cocaine; moreover, they seem to indicate that both DA D1 and DA D2 receptor subtypes are under such influence.
Przegaliński
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E
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Filip
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M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000633:toxicity; D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D001971:Bromocriptine / Q000633:toxicity; D003042:Cocaine / Q000633:toxicity; D018491:Dopamine Agonists / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; D001971:Bromocriptine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D003042:Cocaine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester