Nifedipine Suppresses Self-Injurious Behaviors in Animals

Abstract

Self-injurious behavior is a common problem in many developmental disorders. The neurobiology of this behavior is not well understood, but the differing behavioral manifestations and associations with different disorders suggest that the underlying biological mechanisms are heterogeneous. The behavioral and biological heterogeneity is also evident in several animal models, where different manifestations can be provoked under different experimental conditions. Identifying commonalities among the different mechanisms is likely to be helpful in the design of treatments useful for the broadest populations of patients. The current studies reveal that nifedipine suppresses self-injurious behavior in 4 unrelated animal models: acute administration of high doses of ±BayK 8644 or methamphetamine in mice, dopamine agonist treatment in rats with lesions of dopamine pathways during early development and repeated administration of pemoline in rats. The effect of nifedipine does not appear to be due to nonspecific mechanisms, such as sedation, since other classes of behaviors are unaffected or exaggerated. These results suggest that nifedipine may target a common biological mechanism in the expression of self-injurious behavior, and they suggest it should be considered in the treatment of self-injury in humans.

Multidisciplinary Assessment and Treatment of Self-Injurious Behavior in Autism Spectrum Disorder and Intellectual Disability: Integration of Psychological and Biological Theory and Approach

“…Psychostimulants such as methylphenidate, methamphetamine, caffeine, BayK 8644, and pemoline appear to affect these pathways, as well (Blake et al 2007). Pemoline is an indirect monoamine agonist that blocks reuptake of DA and .…”

Lesch-Nyhan disease: from mechanism to model and back again

“…The neonatal 6-hydroxydopamine rat model has led to proposals for using D1-dopamine receptor antagonists for self-injurious behavior in LND (Gualtieri and Schroeder, 1991), whereas the BayK 8644 model has led to suggestions regarding the use of L-type calcium channel antagonists (Blake et al, 2006). These and related drugs provide rational choices for clinical trials.…”

Functional Neuroanatomy of Secondary Self-Injurious Behavior

“…For example, loss of MeCP2, a transcriptional regulator, from a subset of forebrain GABAergic neurons can recapitulate the compulsive and self-injurious features of Rett syndrome, a disease with a clinical presentation that often mimics features of severe autism [66]. In a very different model type without genetic manipulation, mice injected with stimulants, dopamine agonists, or calcium-channel agonists have been observed to exhibit SSIB, such as self-biting [67,68]. There is even a behavioral model of SSIB in which normal monkeys that have shown evidence of SSIB traits convert to more fulminant SSIB when placed in stressful environments [69].…”