Drug-induced Self-biting in Rodents: Implications for the Lesch-nyhan Syndrome

Self-mutilation is a serious clinical problem. In humans selfmutilation is a characteristic of the Lesch-Nyhan syndrome and the de Lange syndrome. Several common drugs have been reported to produce self-biting in animals. The purpose of this project is to begin to de­ termine whether drug-induced self-biting in animals shares behavioral or biochemical characteristics with self-biting in the Lesch-Nyhan syndrome. Availability of such an animal model would greatly facilitate develop­ ment of rational therapies and elucidation of neurochemical mechanisms. The Lesch-Nyhan syndrome is the result of a genetic defect in purine metabolism. Purines may function as neural transmitters or pu­ rines may be released along with classical neurotransmitters, or purines may modulate neural transmission. This research is based on the assump­ tion that the self-mutilation which accompanies the Lesch-Nyhan syndrome is the result of a) decreased availability of purlnergic neuroregulators b) Increased amounts of hypoxanthine in the central nervous system c) a combination of the above. •> The behavioral characteristics of three types of drug-induced self-biting (caffeine, clonidlne, and pemoline) were examined. Then various purines were administered in an attempt to modify drug-induced self-biting. Pemoline was administered orally to rats in doses of 140 and 220 rag/kg. Self-biting of the medial digits and dorsomedial aspect of the foreleg was commonly observed and appeared to result from intense grooming of these areas. The severity of self-biting was dose-related