[C]()-Rolipram positron emission tomography detects DISC1 inhibition of phosphodiesterase type 4 in live locus-impaired mice.

Although still a matter of controversy, disrupted in schizophrenia protein 1 (DISC1) was suggested as a potential inhibitor of phosphodiesterase 4 (PDE4). We used locus impairment (LI) mice to investigate the interaction between PDE4 and DISC 1 and . C-Rolipram binding was measured by PET in LI ( = 11) and C57BL/6 wild-type (WT,  = 9) mice. C-Rolipram total distribution volumes () were calculated and corrected for plasma-free fraction () measured in a separate group of LI ( = 6) and WT ( = 7) mice. PDE4 enzyme activity was measured using samples of cerebral cortices from groups of LI ( = 4), heterozygote ( = 4), and WT ( = 4) mice. LI mice showed a 41% increase in (18 ± 6 vs. 13±4 mL/cm,  = 0.04) compared to WT mice. / showed a 73% significant increase (90 ± 31 vs. 52 ± 15 mL/cm,  = 0.004) in LI compared to WT mice. PDE4 enzymatic activity assay confirmed in vivo findings showing significant group differences ( < 0.0001). In conclusion, PDE4 activity was increased in the absence of critical DISC1 protein isoforms both in vivo and in vitro. Additionally, C-Rolipram PET was sensitive enough to assess altered PDE4 activity caused by PDE4-DISC1 interaction.