title: Transplantation of human retinal pigment epithelial cells in the nucleus accumbens of cocaine self-administering rats provides protection from seeking.
abstract: Chronic exposure to drugs and alcohol leads to damage to dopaminergic neurons and their projections in the 'reward pathway' that originate in the ventral tegmental area (VTA) and terminate in the nucleus accumbens (NAc). This damage is thought to contribute to the signature symptom of addiction: chronic relapse. In this study we show that bilateral transplants of human retinal pigment epithelial cells (RPECs), a cell mediated dopaminergic and trophic neuromodulator, into the medial shell of the NAc, rescue rats with a history of high rates of cocaine self-administration from drug-seeking when returned, after 2 weeks of abstinence, to the drug-associated chamber under extinction conditions (i.e., with no drug available). Excellent survival was noted for the transplant of RPECs in the shell and/or the core of the NAc bilaterally in all rats that showed behavioral recovery from cocaine seeking. Design based unbiased stereology of tyrosine hydroxylase (TH) positive cell bodies in the VTA showed better preservation (p<0.035) in transplanted animals compared to control animals. This experiment shows that the RPEC graft provides beneficial effects to prevent drug seeking in drug addiction via its effects directly on the NAc and its neural network with the VTA.
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: kvenkiteswaran@hmc.psu.edu.
authors.forename: Kala
authors.initials: K
authors.lastname: Venkiteswaran
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: dna113@psu.edu.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Alexander
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: mpuhl@mclean.harvard.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Puhl
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: Anand.Rao.721@gmail.com.
authors.forename: Anand
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: apiquet@partners.org.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Piquet
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: jennifer.e.nyland.vol@mail.mil.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Nyland
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: msubramanian@wesleyan.edu.
authors.forename: Megha P
authors.initials: MP
authors.lastname: Subramanian
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: puja.iyer@gmail.com.
authors.forename: Puja
authors.initials: P
authors.lastname: Iyer
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: mmboisve@ucsd.edu.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Boisvert
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: ennedder@gmail.com.
authors.forename: Erin
authors.initials: E
authors.lastname: Handly
authors.affiliation: Department of Neurology, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: tsubram@yahoo.com.
authors.forename: Thyagarajan
authors.initials: T
authors.lastname: Subramanian
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: psg6@psu.edu.
authors.forename: Patricia Sue
authors.initials: PS
authors.lastname: Grigson
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D003216:Conditioning, Operant / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D059290:Dopaminergic Neurons; D058999:Drug-Seeking Behavior / Q000502:physiology; D004847:Epithelial Cells; D005108:Extinction, Psychological / Q000502:physiology; D006801:Humans; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000637:transplantation*; D012168:Retinal Pigments; D012201:Reward; D012646:Self Administration; D019966:Substance-Related Disorders / Q000517:prevention & control*; D017557:Ventral Tegmental Area / Q000187:drug effects
chemical_list: D012168:Retinal Pigments; D003042:Cocaine; D004298:Dopamine
keywords: Addiction; Cocaine; RPEC; Rat; Reinstatement; Transplant