Attenuation of ethanol-induced ataxia by α4β2 nicotinic acetylcholine receptor subtype in mouse cerebellum: A functional interaction
| Autor: | M. Saeed Dar, Najla Taslim, Salim S. Al-Rejaie |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Agonist Nicotine Cerebellum medicine.medical_specialty Ataxia Microinjections medicine.drug_class Blotting Western Central nervous system Receptors Nicotinic Stereotaxic Techniques Mice Internal medicine medicine Animals Nicotinic Agonists Postural Balance Acetylcholine receptor Membranes Ethanol Chemistry General Neuroscience Antagonist Central Nervous System Depressants Dihydro-beta-Erythroidine Nicotinic acetylcholine receptor medicine.anatomical_structure Endocrinology Oligodeoxyribonucleotides medicine.symptom medicine.drug |
| Zdroj: | Neuroscience. 157:204-213 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2008.08.046 |
| Popis: | Many epidemiological studies support the notion that people who drink alcohol also smoke cigarettes and vice versa thereby suggesting a possible functional interaction between these two most widely used psychoactive substances. We have earlier demonstrated that direct intracerebellar (ICB) microinfusion of nicotine dose-dependently antagonizes ethanol-induced ataxia and further that this antagonism occurs in a glutamate-nitric oxide-cyclic guanylyl monophosphate (cGMP) sensitive manner. The present study was designed to determine the possible involvement of specific nicotinic acetylcholine receptor (nAChR) subtype alpha(4)beta(2) in nicotine-induced attenuation of ethanol ataxia. Using the Rotorod test and direct ICB microinfusion technique in stereotaxically cannulated CD-1 male mice, we performed the Rotorod test following ICB administration of the alpha(4)beta(2)-selective agonist, (E)-N-methyl-4-(3-pyridinyl)-3-buten-1-amine (RJR-2403; 31.25, 62.5, 125 ng) on ethanol (2 g/kg; i.p.) ataxia at 15, 30, 45, 60 min post-ethanol injection. RJR-2403 dose-dependently attenuated ethanol ataxia suggesting a role of alpha(4)beta(2) subtype in ameliorating ethanol-induced ataxia. Pretreatment with ICB dihydro-beta-erythroidine (DHbetaE: 125, 250, 500, 750 ng), a potent alpha(4)beta(2)-selective antagonist, significantly reduced RJR-2403's effect further supporting the alpha(4)beta(2) involvement. DHbetaE (ICB) also antagonized ICB nicotine-induced attenuation of ethanol ataxia again reinforcing the role of alpha(4)beta(2) subtype. Additional evidence for the role of alpha(4)beta(2) subtype was provided when ICB alpha(4)beta(2) antisense oligodeoxynucleotide treatment markedly antagonized RJR 2403-induced attenuation of ethanol ataxia compared with missense-treated animals. This was confirmed with an associated decrease in the expression of alpha(4)beta(2) subtypes indicated by immunoblot experiments. In conclusion, the results of the present investigation support an important role of alpha(4)beta(2) nAChR subtype in the expression of nicotine-induced attenuation of ethanol ataxia. |
| Databáze: | OpenAIRE |
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