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In frontal cortex, the main brain area affected in PiD, A<jats:sub>1<\/jats:sub>Rs, determined by radioligand binding, Western blotting and real\u2010time PCR assays, were significantly increased in PiD samples, suggesting up\u2010regulation of this receptor. AC activity was determined in basal and stimulated conditions via stimulatory guanine nucleotide binding proteins (Gs) using GTP, or directly with forskolin. Basal AC activity was reduced in brains from PiD cases. This agrees with the decrease in AC type\u2003I (AC\u2003I) level detected by Western blotting. However, inhibition of forskolin\u2010stimulated AC activity by a selective A<jats:sub>1<\/jats:sub>R agonist was significantly increased in brains from PiD. In occipital cortex, adenosine A<jats:sub>1<\/jats:sub>R numbers were similar in control and PiD cases, and no significant differences were found in A<jats:sub>1<\/jats:sub>R\u2010mediated AC inhibition. 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