Transplantation of human retinal pigment epithelial cells in the nucleus accumbens of cocaine self-administering rats provides protection from seeking

•Some out bred Sprague–Dawley rats take more cocaine than others.•High drug-takers show greater reinstatement of cocaine seeking than Low drug-takers.•RPEC grafts into NAc rescue High drug-takers from reinstatement after 14d abstinence.•RPEC grafts into NAc preserve DA cell bodies in the VTA of High drug-taker rats.•RPEC grafts in NAc protect DA cells in VTA and rescue High takers from reinstatement.

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.