PT  - JOURNAL ARTICLE
AU  - Thomas J. Gould
AU  - Paula C. Bickford
TI  - Age-Related Deficits in the Cerebellar <em>Beta</em>Adrenergic Signal Transduction Cascade in Fischer 344 Rats
DP  - 1997 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 965--971
VI  - 281
IP  - 2
4099  - http://jpet.aspetjournals.org/content/281/2/965.short
4100  - http://jpet.aspetjournals.org/content/281/2/965.full
SO  - J Pharmacol Exp Ther1997 May 01; 281
AB  - Localization of age-related deficits in the cerebellarbeta adrenergic signal transduction cascade were investigated electrophysiologically using forskolin (FORSK) and adenosine-3′,5′-cyclic monophosphothioate Sp-isomer (Sp-cAMPS) appliedvia pressure ejection from extracellular multibarreled glass electrodes to activate the transduction cascade. In young rats, 100 μM FORSK activated AC, and 100 μM Sp-cAMPS activated protein kinase A; thus, both increased GABAergic inhibition of Purkinje cell firing. In aged rats, however, 100 μM FORSK was unable to increase GABAergic inhibition of Purkinje cell firing. In addition, 1 mM 7β-decacetyl-7β-(γ-N-methylpiperazino)butyryl-forskolin, an analog of FORSK, was also unable to increase GABAergic inhibition in aged rats. In contrast, Sp-cAMPS was able to increase GABAergic inhibition in aged rats, but higher doses were required than in young rats. Isoproterenol (ISO), a beta adrenergic agonist, was ineffective in increasing GABAergic inhibition of Purkinje firing in aged rats when tested alone, but ISO was effective in increasing Purkinje cell inhibition when ISO was tested with Sp-cAMPS. The results of this experiment indicate that one age-related deficit in the cerebellar beta adrenergic system occurs at the level of protein kinase A activation. The American Society for Pharmacology and Experimental Therapeutics