title: NCAM signaling mediates the effects of GDNF on chronic morphine-induced neuroadaptations.
abstract: Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for midbrain dopamine (DA) neurons, while the DA neurons in the ventral tegmental area (VTA) is a crucial part of the neural circuits associated with drug addiction. Recently, more and more evidence suggests that GDNF plays an important role in negatively regulating the neuroadaptations induced by chronic exposure to drugs, which was thought to be the neurobiological basis of drug addiction, but the underlying mechanism is still unknown. More recently, the neural cell adhesion molecule (NCAM), which plays an important role in the process of neural plasticity, has been identified as an alternative signaling receptor for GDNF. The purpose of this study was to investigate whether NCAM was involved in the effects of GDNF on the neuroadaptations induced by chronic morphine exposure. Immunostaining results showed that NCAM was widely expressed in the VTA of rats, including all the DA neurons. The results also showed that the phosphorylation of NCAM-associated FAK, but not the total NCAM, was upregulated by GDNF, and this upregulation was inhibited by pre-treatment with the NCAM function-blocking antibody. Moreover, pre-treatment with the antibody could antagonize the effect of GDNF on inhibiting the neuroadaptations induced by chronic morphine exposure, including the decreases of the number and length of neurites and the size of cell bodies of VTA dopamine neurons, as well as the increase of tyrosine hydroxylase in the VTA dopamine neurons. These results suggest that NCAM signaling is involved in the negative regulatory effects of GDNF on chronic morphine-induced neuroadaptations.
authors.affiliation: Jiangsu Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Junping
authors.initials: J
authors.lastname: Cao
authors.forename: Suming
authors.initials: S
authors.lastname: Zhang
authors.forename: Cunjin
authors.initials: C
authors.lastname: Wang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Song
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
authors.forename: Licai
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015854:Up-Regulation; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D009294:Narcotics; D019006:Neural Cell Adhesion Molecules; D009020:Morphine; D051416:Focal Adhesion Protein-Tyrosine Kinases