Dopaminergic and glutamatergic interactions in the expression of self-injurious behavior.
Self-injurious behavior occurring in persons with severe mental retardation is a clinically significant and poorly understood problem. Multiple neurotransmitter systems have been implicated in the pathogenesis of this behavior, particularly dopaminergic, opioidergic, and serotonergic systems. Pemoline, a central stimulant, administered systemically at high doses reliably produces self-biting behavior in the rat. The systemic bolus of pemoline produces sustained neostriatal levels of pemoline for over 24 h in a continuous infusion paradigm. Studies of the effect of cortical lesions on pemoline-mediated behaviors reveal that cortical damage, as is common in profound mental retardation, lowers the threshold for pemoline-induced self-biting behavior. Data from the corticostriatal slice suggests that sustained exposure to pemoline produces a shift in N-methyl-D-aspartate receptor-mediated responses rendering them more susceptible to dopaminergic enhancement. Thus, dopaminergic and glutamatergic interactions appear to play an important role in the development and expression of self-biting in the pemoline model.
UCLA Neuropsychiatric Institute, Los Angeles, CA 90024-1759, USA.
B H
BH
King
H C
HC
Cromwell
H T
HT
Lee
S P
SP
Behrstock
T
T
Schmanke
N T
NT
Maidment
D000818:Animals; D000697:Central Nervous System Stimulants; D002540:Cerebral Cortex / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D004347:Drug Interactions; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D010389:Pemoline / Q000493:pharmacokinetics / Q000494:pharmacology; D016728:Self-Injurious Behavior / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
D000697:Central Nervous System Stimulants; D018698:Glutamic Acid; D010389:Pemoline; D004298:Dopamine