Editors' ChoiceAddiction

GDNF Prevents Addiction

STKE  02 May 2000:
Vol. 2000, Issue 30, pp. tw1
DOI: 10.1126/stke.2000.30.tw1

Drugs of abuse, such as cocaine and morphine, induce a type of synaptic plasticity in the mesolimbic dopamine system. Messer et al. determined that glial-derived neurotrophic factor (GDNF) was involved in the biochemical and behavioral changes associated with chronic drug exposure. Their data show that infusion of GDNF can prevent or reverse the biochemical changes induced by chronic morphine or cocaine exposure. Furthermore, endogenous GDNF activity was required for biochemical and behavioral changes caused by drug exposure. Morphine and cocaine decreased signaling by the GDNF pathway by decreasing the levels of phosphorylated Ret, the kinase activated by the GDNF receptor. Thus, the GDNF signaling pathway provides a potential target for development of treatments for addiction.

Messer, C.J., Eisch, A.J., Carlezon, Jr., W.A., Whisler, K., Shen, L., Wolf, D.H., Westphal, H., Collins, F., Russell, D.S., and Nestler, E.J. (2000) Role for GDNF in biochemical and behavioral adaptations to drugs of abuse. Neuron 26: 247-257. [Online Journal]