Bromocriptine and quinpirole, but not 7-OH-DPAT or SKF 38393, potentiate the inhibitory effect of L-NAME on ethanol-induced locomotor activity in mice.
The effects of N(G)-nitro- l-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, SKF 38393, bromocriptine (BRM), quinpirole (QPR) and 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT), dopamine receptor agonists, and combinations of the dopamine agonists and L-NAME on ethanol-induced locomotor activity in adult male Swiss-Webster mice were investigated. The mice were given ethanol (0.5-2 g/kg), L-NAME (15-60 mg/kg), SKF 38393 (5-20 mg/kg), BRM (2.5 and 5 mg/kg), QPR (0.25 and 0.5 mg/kg), 7-OH-DPAT (0.5 and 1.0 mg/kg), a combination of l-arginine (1 g/kg) and L-NAME (60 mg/kg), combinations of SKF 38393, BRM, QPR or 7-OH-DPAT with L-NAME (60 mg/kg) or ethanol (0.5 g/kg) and saline or vehicle by i.p. injection. Triple combinations (dopaminergic agonist, 60 mg/kg L-NAME and 0.5 g/kg ethanol) were also given. Locomotor activity was measured for 30 min immediately following ethanol injections. Ethanol (0.5 g/kg) significantly increased locomotor activity. L-NAME, BRM, QPR and 7-OH-DPAT blocked the ethanol (0.5 g/kg)-induced locomotor hyperactivity dose dependently and at doses that did not affect locomotor activity in naive mice when administered alone. The inhibitory effects of L-NAME (60 mg/kg) were not prevented by pretreatment with l-arginine. BRM and QPR, but not 7-OH-DPAT, significantly and dose-dependently potentiated the inhibitory effect of L-NAME. Our results suggest that L-NAME inhibits ethanol-induced locomotor hyperactivity in mice by a mechanism not involving NO. The inhibitory effect of L-NAME may be related to the activation of presynaptic dopamine D(2) receptors rather than dopamine D(3) receptors.
Uzbay
I Tayfun
IT
Department of Medical Pharmacology, Psychopharmacology Research Unit, Faculty of Medicine, Gülhane Military Medical Academy, 06018 Etlik, Ankara, Turkey. tuzbay@gata.edu.tr
Kayir
Hakan
H
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D004791:Enzyme Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D009569:Nitric Oxide; D001971:Bromocriptine; D000431:Ethanol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001120:Arginine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D019331:NG-Nitroarginine Methyl Ester