Abstract Details

Title Dopaminergic Grafts Prevent Risk Of Secondary Parkinsonism In Cocaine Self-administering Rats

Topic Movement Disorders

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-007

Objective

Assess effects of dopamine depletion in chronic high dose cocaine self-administering rats and its rescue following dopaminergic cell transplantation to prevent secondary parkinsonism.

Background Refractory cocaine and amphetamine addicts have increased vulnerability to develop parkinsonism. Refractory drug addiction is associated with high rates of incarcerations, emergency hospitalizations and mortality. Our recent work using operant conditioned high cocaine self administering rats showed >50% loss of dopaminergic neurons in ventral tegmental area (VTA). In this model, transplantation of dopamine and growth factor secreting human embryonic retinal pigment epithelial cells (heRPEC) bilaterally into the nucleus accumbens (NAc) resulted in rescue of dopaminergic cell loss in the VTA and significant amelioration of the risk for relapse/drug seeking. We tested whether these animals will have better preservation of substantia nigra pars compacta (SNpc) neurons and reduced risk for parkinsonism.

Design/Methods

Eighty-four Sprague-Dawley rats were operant conditioned to a drug seeking behavioral using positive reinforcement and intra jugular delivery of cocaine. One half of the high (n=22) cocaine taking rats received bilateral intra NAc stereotactic transplants of heRPEC. and the other half (n=16) received matching controls grafts. Remaining animals served as controls. Extensive drug seeking and motor behavioral assessments along with design based stereological estimates of immunohistology were outcome measures.

Results Significant reduction in drug seeking was noted in grafted animals (mean 26 infusion attempts versus 35 in controls). Preservation of VTA dopaminergic neurons in unbiased stereological counts was noted in heRPEC grafted animals (p < 0.035). Similarly, better preservation of SNpc dopaminergic neurons was noted in heRPEC grafted animals without any parkinsonism. Control surgery treated animals had significant neuronal loss in both VTA and in the SNpc.

Conclusions

Our results support the use of bilateral heRPEC grafts into NAc in refractory high drug taking cocaine users. In addition, this therapy appears to prevent the risk of secondary parkinsonism.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Alex Kim, MD	Dr. Kim has nothing to disclose.
Megha Subramanian	No disclosure on file
Thyagarajan Subramanian, MD, MBBS, FAAN (University of Toledo)	Dr. Subramanian has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurocrine. Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Supernus. Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Subramanian has received research support from National Institutes of Health. The institution of Dr. Subramanian has received research support from Ann and Phillip Gladfetler III Foundation. The institution of Dr. Subramanian has received research support from Department of Defense . Dr. Subramanian has received publishing royalties from a publication relating to health care. Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with National Institutes of Health.
	No disclosure on file

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