Transplantation of glial cell line-derived neurotrophic factor-expressing cells into the striatum and nucleus accumbens attenuates acquisition of cocaine self-administration in rats.
Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), may play a role in drug-induced biochemical and behavioural adaptations that characterize addiction. We found that GDNF mRNA levels are lower in the striatum of rats that chronically self-administered cocaine. Therefore, we examined the effect of transplanted cells used as a biodelivery system for GDNF on cocaine self-administration in rats. A human astrocyte-like cell line, which produces and excretes GDNF, was transplanted into the striatum and nucleus accumbens of rats. These rats showed a significantly lower number of active lever presses in the cocaine self-administration paradigm compared with control rats. Moreover, rats that received a chronic infusion of GDNF via a micro-osmotic pump also exhibited weak cocaine self-administration. Therefore, we conclude that exogenous augmentation of GDNF repositories may be useful in suppressing cocaine self-administration.
Green-Sadan
Tamar
T
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Kinor
Noa
N
Roth-Deri
Ilana
I
Geffen-Aricha
Revital
R
Schindler
Cheryl J
CJ
Yadid
Gal
G
D000818:Animals; D002460:Cell Line / Q000821:virology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007150:Immunohistochemistry; D007260:Infusion Pumps; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000627:therapeutic use; D009457:Neuroglia / Q000378:metabolism / Q000637:transplantation* / Q000821:virology; D009714:Nucleus Accumbens / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012646:Self Administration; D013539:Simian virus 40 / Q000378:metabolism; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D003042:Cocaine