title: Glial cell line-derived neurotrophic factor-conjugated nanoparticles suppress acquisition of cocaine self-administration in rats.
abstract: The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) may have therapeutic potential for preventing and treating cocaine addiction. Previously, we found that transplantation of a GDNF-expressing astrocyte cell line into the striatum and nucleus accumbens attenuates cocaine-seeking behavior in Sprague-Dawley rats. However, as a potential treatment for humans, cell transplantation presents several technical and ethical complications. Nanoparticulate systems are a safe and effective method for introducing exogenous compounds into the brain. Therefore, we examined the effect of GDNF-conjugated nanoparticles microinjected into the striatum and nucleus accumbens on cocaine self-administration in rats. GDNF-conjugated nanoparticles blocked the acquisition of cocaine self-administration compared to control treatments. Furthermore, a cocaine dose response demonstrated that decreased lever response in rats that received GDNF-conjugated nanoparticles persisted after substitution with different cocaine doses. This effect is not due to a non-specific disruption of locomotor or operant behavior, as seen following a water operant task. The current study is one of the first demonstrations that drug-conjugated nanoparticles may be effective in treating brain disorders. These findings suggest that GDNF-conjugated nanoparticles may serve as a novel potential treatment for drug addiction.
authors.affiliation: Neuropharmacology Laboratory, Faculty of Life Sciences and the Leslie and Susan Gonda (Goldshmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Green-Sadan
authors.forename: Y
authors.initials: Y
authors.lastname: Kuttner
authors.forename: T
authors.initials: T
authors.lastname: Lublin-Tennenbaum
authors.forename: N
authors.initials: N
authors.lastname: Kinor
authors.forename: Y
authors.initials: Y
authors.lastname: Boguslavsky
authors.forename: S
authors.initials: S
authors.lastname: Margel
authors.forename: G
authors.initials: G
authors.lastname: Yadid
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003042:Cocaine / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005290:Ferric Compounds / Q000008:administration & dosage*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D008845:Microinjections / Q000379:methods; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000737:chemistry; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D016896:Treatment Outcome
chemical_list: D005290:Ferric Compounds; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C000499:ferric oxide; D003042:Cocaine; D004298:Dopamine