Differential effects of amphetamine and GBR-12909 on orolingual motor function in young vs aged F344/BN rats.

Orolingual motor deficits, such as dysarthria and dysphagia, contribute to increased morbidity and mortality in the elderly. In preclinical studies, we and others have reported age-related decreases in tongue motility in both F344 and F344/BN rats. The fact that these deficits are associated with nigrostriatal dopamine (DA), tissue measures suggest that increasing dopamine function might normalize tongue motility. The purpose of the current study was to determine whether two indirect dopamine agonists with locomotor-enhancing effects, d-amphetamine (amphetamine; 1 and 2 mg/kg) and GBR-12909 (5, 10, and 20 mg/kg), can improve tongue motility in aged F344/BN rats. Young (6 months) and aged (30 months) F344/BN rats licked water from an isometric force disc so that tongue motility (licks/second) and tongue force could be measured as a function of age and drug dose. Consistent with our previous studies, tongue force was greater and tongue motility was lower in the aged group. Tongue motility was increased by amphetamine but not by GBR-12909. Amphetamine decreased peak tongue force, primarily in the young group. GBR-12909 did not affect tongue force. GBR-12909 increased the number of licks/session in the young group but not in the aged group, while amphetamine increased this measure in both groups. These results demonstrate differential effects of these drugs on orolingual motor function and suggest that blocking DA uptake is insufficient to increase tongue motility in aging.

Citation

Susan Smittkamp, Heather Spalding, Hongyu Zhang, John A Stanford. Differential effects of amphetamine and GBR-12909 on orolingual motor function in young vs aged F344/BN rats. Psychopharmacology. 2014 Dec;231(24):4695-701

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PMID: 24923981

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