Researchers report a potential drug target and lead compound for stimulant use disorder. Human studies have identified associations between addiction-related phenotypes and variants in the gene for receptor-type protein tyrosine phosphatase D (PTPRD), a neuronal cell adhesion molecule and synaptic specifier. George Uhl and colleagues found that when mice were allowed to self-administer cocaine, those lacking a copy of the gene for PTPRD did so at significantly lower rates than control mice. The authors identified a chemical analog of 7-butoxy illudalic acid (7-BIA) that selectively inhibited the phosphatase activity of PTPRD in vitro. Treating mice with 7-BIA alone had no apparent behavioral or pathological effects. Mice pretreated with 7-BIA exhibited reduced preference for cocaine-associated places and reduced rates of cocaine self-administration, compared with untreated mice. The effect of 7-BIA treatment on cocaine self-administration was not observed in mice lacking a copy of the PTPRD gene. The results suggest that PTPRD is a potential therapeutic target for cocaine use disorders, and that 7-BIA is a potential therapeutic lead compound for cocaine dependence, according to the authors.
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Article #17-20446: "Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist," by George R. Uhl et al .
MEDIA CONTACT: George R. Uhl, New Mexico VA Health Care System, Albuquerque, NM; tel: 505-265-1711 x 4712; e-mail: George.Uhl@va.gov
Proceedings of the National Academy of Sciences