We first demonstrated that injection of AAV-MOR increased MOR immunoreactivity in brain. Using cell culture, we found that AAV-MOR transfection can increase MOR binding and MOR immunoreactivity in 293 cells. These data suggest that treatment with AAV-MOR enhances MOR expression in vivo and in vitro. AAV-MOR or AAV-GFP was then injected into the nucleus Accumbens (NAc) or ventral tegmental area (VTA) of adult C57/BL6 mice. Two weeks after viral infection, animals received methamphetamine or saline for 5 consecutive days. Repeated administration of methamphetamine progressively increased locomotor activity;this sensitization reaction was attenuated by NAc AAV-MOR pretreatment. In contrast, administration of AAV-MOR to VTA enhanced methamphetamine sensitization. AAV-MOR significantly enhanced DA levels in VTA after VTA infection but reduced DOPAC/DA turnover in the NAc after NAc injection. Our data suggest a differential modulation of methamphetamine sensitization by overexpression of MOR in NAc and VTA.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$67,594
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Reiner, David J; Yu, Seong-Jin; Shen, Hui et al. (2014) 9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons. Neurotox Res 25:248-61
Luo, Yu; Shen, Hui; Liu, Hua-Shan et al. (2013) CART peptide induces neuroregeneration in stroke rats. J Cereb Blood Flow Metab 33:300-10
Henderson, Mark J; Richie, Christopher T; Airavaara, Mikko et al. (2013) Mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion and cell surface binding are modulated by KDEL receptors. J Biol Chem 288:4209-25