Fig. 1.

Pathways implicated in tolerance that converge on Src. Neurons contain high levels of c-Src.²¹ Recent studies have identified several pathways that converge on Src, their inhibition reduces morphine tolerance,⁶,³⁸–⁴² potentially implicating the non-receptor tyrosine kinase as a hub in this process. Red spots represent targets of Src-mediated phosphorylation.²⁴,²⁵,⁴³ μ Receptors (grey), the chemokine receptor type 4 (CXCR4), the leptin receptor (LEPR), N-methyl D-aspartate receptors (NMDA-R) and platelet derived growth factor receptor β (PDGF-β) are depicted in grey, red, green, dark blue and light blue, respectively. β-Arrestin2 (β-arr2), Src kinase (Src), c-Jun N-terminal kinase (JNK), mechanistic target of rapamycin (mTOR) and N-type Ca²⁺ channels (Ca_V2.2) are depicted in green, pink, orange, yellow and light blue, respectively.