Objective: To investigate the inhibitory effect of antisense oligonucleotides (ODN) on dopamine transporter (DAT) in rats and observe the response of the rats to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Methods: The cannula was implanted in the substantia nigra compacta under a rat stereotaxic device, through which drugs were used. The rats with successful operation were divided randomly into four groups, and received injection of antisense, sense, missense oligonucleotides and saline respectively, in the substantia nigra compacta of each rat via the cannula, followed by MPTP (30 mg/kg) injection. Behavior of the rats was observed and immunohistochemistry was carried out to check the expression of DAT and apoptosis of dopamine cell.
Results: The expression of DAT (positive unit, PU) in the substantia nigra compacta in rats was 6.65+/- 1.67 in the antisense ODN group, 12.41+/- 2.46 in saline group, 11.45+/- 1.17 in sense ODN group, and 10.35+/- 2.89 in missense ODN group. The expression of DAT was lower in the antisense ODN group than that of the other three groups (P< 0.01). The rotation of the rats induced by apomorphine was slower than that of the other three groups(P< 0.05). The apoptotic cells (21.4+/- 5.6) in the antisense ODN group (200x ) were less than that of the other three groups (61.6+/- 19.7, 56.5+/- 16.3, 52.2+/- 12.5 respectively), (P< 0.01).
Conclusion: The expression of DAT can be inhibited effectively by the antisense ODN, and the response of the rats to the MPTP was reduced upon DAT inhibition.