Pharmacologic thresholds for self-injurious behavior in a genetic mouse model of Lesch-Nyhan disease.

Congenital deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) causes Lesch-Nyhan disease in humans, which is associated with severe and recurrent self-injurious behavior (SIB). The HPRT-deficient knockout mouse model, however, does not display this unusual behavior. The present studies tested whether these mice might be more vulnerable to pharmacologic agents known to cause SIB in normal rodents, including clonidine, Bay K 8644, GBR 12909, methamphetamine, pemoline and caffeine. The results provided three conclusions. First, normal mice did not display SIB using some drugs known to provoke the behavior in rats (GBR 12909, caffeine), indicating important species differences in the expression of the behavior. Second, the C57BL/6J mice did not display SIB using drugs effective for other strains of mice (methamphetamine, pemoline), indicating important strain differences in expression of the behavior. Finally, there was no evidence that the HPRT-deficient mice were more susceptible to SIB when it occurred (clonidine, Bay K 8644).