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Antagonism of ethanol ataxia by intracerebellar nicotine: possible modulation by mouse cerebellar nitric oxide and cGMP.
- Source :
-
Brain research bulletin [Brain Res Bull] 2006 Mar 31; Vol. 69 (2), pp. 187-96. Date of Electronic Publication: 2005 Dec 20. - Publication Year :
- 2006
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Abstract
- We have reported previously that intracerebellar nicotine attenuates ethanol ataxia via nicotinic-cholinergic receptors. We report now that attenuation of ethanol ataxia by intracerebellar nicotine is modulated by cerebellar nitric oxide-guanylyl cyclase (GC) messenger system. Intracerebellar microinfusion of SNP (sodium nitroprusside, a nitric oxide donor; 15, 30, and 60 pg) and SMT (S-methylisothiourea; 70, 140, and 280 fg; an inhibitor of inducible nitric oxide synthase), significantly enhanced and reduced, respectively, intracerebellar nicotine-induced attenuation of ethanol ataxia in a dose-related manner. Similarly, intracerebellar isoliquiritigenin (an activator of GC; 1, 2, and 4 pg) and ODQ (1H [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, an inhibitor of GC; 375, 750, and 1500 fg), significantly enhanced and reduced, respectively, intracerebellar nicotine-induced attenuation of ethanol ataxia in a dose-related fashion. These results suggest that the functional interaction between nicotine and ethanol may involve modulation by cerebellar nitric oxide and cGMP. Intracerebellar microinfusion of isoliquiritigenin (4, 8, and 16 pg) in the absence of nicotine significantly attenuated ethanol ataxia dose-dependently indicating a tonic involvement of cGMP in ethanol ataxia. Finally, intracerebellar nicotine (5 ng) significantly increased and ethanol 2 g/kg i.p. decreased levels of total cerebellar nitrite+nitrate (NOx) which were functionally correlated with ethanol ataxia and its attenuation by intracerebellar nicotine. The ethanol-induced decrease in NOx was significantly antagonized by intracerebellar nicotine. The NOx data further supported an involvement of nitric oxide in the behavioral interaction between nicotine and ethanol. Overall, the results of the present investigation demonstrate a functional correlation between cerebellar nitric oxide messenger system and the behavioral interaction between nicotine and ethanol.
- Subjects :
- Alcohol-Induced Disorders, Nervous System enzymology
Alcohol-Induced Disorders, Nervous System physiopathology
Animals
Ataxia chemically induced
Ataxia physiopathology
Central Nervous System Depressants pharmacology
Cerebellum metabolism
Cerebellum physiopathology
Cyclic GMP antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Interactions physiology
Enzyme Inhibitors pharmacology
Male
Mice
Neurons drug effects
Neurons metabolism
Nicotinic Agonists pharmacology
Nitric Oxide Donors
Nitric Oxide Synthase Type II antagonists & inhibitors
Nitric Oxide Synthase Type II metabolism
Second Messenger Systems drug effects
Second Messenger Systems physiology
Tobacco Use Disorder enzymology
Tobacco Use Disorder physiopathology
Ataxia drug therapy
Cerebellum drug effects
Cyclic GMP metabolism
Ethanol pharmacology
Nicotine pharmacology
Nitric Oxide biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0361-9230
- Volume :
- 69
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Brain research bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 16533669
- Full Text :
- https://doi.org/10.1016/j.brainresbull.2005.12.002