Depletion of D3 dopamine receptor affects methamphetamine-induced expression patterns of Pde4b and Atf3

The role of the D3 dopamine receptor (D3R) and the specific molecular mechanisms underlying the regulation of D3R via the cAMP signaling pathway in methamphetamine (METH) addiction are still unclear. Here, we measured changes in Pde4b and Atf3 in the cAMP signaling pathway of dopaminergic system components, including the nucleus accumbens (NAc), caudate putamen (CPu) and hippocampus (Hip), in D3R knockout mice(D3R-/-) 1 h and 24 h after METH-induced behavioral sensitization. We found that knocking out D3R attenuated METH-induced behavioral sensitization, and Pde4b and Atf3 exhibited different expression patterns in brain regions in response to METH. Knocking out D3R suppressed the METH-induced increase in Pde4b in the Hip of mice 24 h after the final METH injection and augmented the METH-induced increase in Atf3 in the CPu of mice 1 h after the final METH injection. Our study suggests that D3R knockout controls METH-induced behavioral sensitization via regulation of Pde4b and Atf3 in different brain regions. Furthermore, the responses of Pde4b and Atf3 to METH exposure depend on the specific region of the brain involved.