Intrastriatal Ro15-4513 functionally antagonizes ethanol-induced motor incoordination and striatal adenosinergic modulation of ethanol-induced motor incoordination in rats. 1994

Z H Meng, and M S Dar
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina.

To study the role of the striatum in modulating the effects of adenosine agonists and benzodiazepine inverse agonists on acute ethanol-induced motor impairment, we evaluated the effect of direct intrastriatal Ro15-4513 [0.625, 1.25 and 2.5 ng], a partial inverse agonist of benzodiazepine receptor, on ethanol-induced motor incoordination. A significant and nearly dose-dependent antagonism by Ro15-4513 was observed, which suggests involvement of the striatum in ethanol-induced motor incoordination. No effect of IST Ro15-4513 on motor incoordination induced by Na-pentobarbital (10 mg/kg, i.p.) was noted, indicating the selectivity of the antiethanol action of Ro15-4513. The IST adenosine agonist N6-cyclohexyladenosine (CHA) markedly accentuated ethanol-induced motor incoordination in a dose-related manner, suggesting a striatal adenosinergic modulation of ethanol-induced motor incoordination. The IST Ro15-4513 also significantly antagonized the accentuating effects of CHA on ethanol-induced motor incoordination. No change in normal motor coordination was observed after IST CHA or Ro15-4513 when followed by saline administration instead of ethanol. No accentuating effect by intrahippocampal CHA on ethanol-induced motor incoordination was seen, which suggests the selectivity of striatal adenosinergic modulation of ethanol-induced motor incoordination. There was no significant radioactivity present in the systemic circulation, in the CSF or in brain areas other than striatum after intrastriatal [3H]Ro15-4513 or [3H]CHA and ethanol injection. Data obtained so far support the involvement of striatum in ethanol's ataxia as well as striatal adenosinergic modulation of the central effect(s) of ethanol, possibly through Ro15-4513-sensitive mechanism(s).

UI MeSH Term Description Entries
D008297 Male Males
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000241 Adenosine A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Adenocard,Adenoscan
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001259 Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions. Coordination Impairment,Dyssynergia,Incoordination,Ataxia, Appendicular,Ataxia, Limb,Ataxia, Motor,Ataxia, Sensory,Ataxia, Truncal,Ataxy,Dyscoordination,Lack of Coordination,Tremor, Rubral,Appendicular Ataxia,Appendicular Ataxias,Ataxias,Ataxias, Appendicular,Ataxias, Limb,Ataxias, Motor,Ataxias, Sensory,Ataxias, Truncal,Coordination Impairments,Coordination Lack,Impairment, Coordination,Impairments, Coordination,Incoordinations,Limb Ataxia,Limb Ataxias,Motor Ataxia,Motor Ataxias,Rubral Tremor,Rubral Tremors,Sensory Ataxia,Sensory Ataxias,Tremors, Rubral,Truncal Ataxia,Truncal Ataxias
D001386 Azides Organic or inorganic compounds that contain the -N3 group. Azide
D001569 Benzodiazepines A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring. Benzodiazepine,Benzodiazepine Compounds
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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