Evidence that lack of brain dopamine during development can increase the susceptibility for aggression and self-injurious behavior by influencing D1-dopamine receptor function.
1. Lesch-Nyhan disease has a defined neurological lesion that is accompanied by abnormal motor function, aggression and self-injurious behavior. 2. The dopamine deficiency in Lesch-Nyhan disease has been modelled by destroying dopamine-containing neurons in neonatal rats with 6-hydroxydopamine. 3. Because D1-dopamine antagonists will block self-injurious behavior induced by L-DOPA in neonatal-6-OHDA-lesioned rats, D1-dopamine antagonists are proposed as a potential therapy for aggression and self-injurious behavior in patients with these symptoms. 4. The determination that the drug SCH-12679, which exhibited effectiveness against aggressiveness in mentally retarded patients, is a D1-dopamine antagonist supports the view that new D1-dopamine antagonists being developed will be an effective therapy for some types of aberrant behavior in this population.
Breese
G R
GR
Brain and Development Research Center, University of North Carolina, School of Medicine, Chapel Hill.
Criswell
H E
HE
Mueller
R A
RA
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000374:Aggression; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D002648:Child; D002657:Child Development; D004298:Dopamine / Q000172:deficiency* / Q000502:physiology; D018492:Dopamine Antagonists; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D007926:Lesch-Nyhan Syndrome / Q000503:physiopathology* / Q000523:psychology; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D014754:Violence
D014151:Anti-Anxiety Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C001016:trimopam; D004298:Dopamine