Dopamine re‐uptake inhibitor GBR‐12909 induction of aberrant behaviors in animal models of dopamine dysfunction

Many individuals with mental retardation exhibit chronic aberrant behaviors (CABs) that includes hyperactive, stereotyped, aggressive, and self‐injurious behaviors. Brain imaging studies have found that several of these individuals have abnormalities in their dopaminergic neurotransmitter systems th...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of developmental neuroscience Vol. 20; no. 3-5; pp. 323 - 333
Main Authors:	Loupe, Pippa S., Bredemeier, Jonna D., Schroeder, Stephen R., Tessel, Richard E.
Format:	Journal Article
Language:	English
Published:	United States 01-06-2002
Subjects:	6‐OHDA Animals Animals, Newborn Behavior, Animal - drug effects Behavior, Animal - physiology Cerebral Cortex - drug effects Cerebral Cortex - metabolism Child Developmental Disabilities - complications Developmental Disabilities - physiopathology Disease Models, Animal Dopamine - metabolism Dopamine Plasma Membrane Transport Proteins Dopamine Uptake Inhibitors - pharmacology Female GBR‐12909 Humans Hyperkinesis - chemically induced Hyperkinesis - etiology Hyperkinesis - physiopathology MAM Membrane Glycoproteins Membrane Transport Proteins - drug effects Membrane Transport Proteins - metabolism Mental Disorders - chemically induced Mental Disorders - etiology Mental Disorders - physiopathology Neostriatum - drug effects Neostriatum - metabolism Neostriatum - physiopathology Nerve Tissue Proteins Norepinephrine - metabolism Piperazines - pharmacology Pregnancy Rats Rats, Sprague-Dawley Receptors, Dopamine - drug effects Receptors, Dopamine - metabolism Rett syndrome Self-Injurious Behavior - chemically induced Self-Injurious Behavior - etiology Self-Injurious Behavior - physiopathology Self‐injurious behavior Serotonin - metabolism Stereotyped Behavior - drug effects Stereotyped Behavior - physiology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Many individuals with mental retardation exhibit chronic aberrant behaviors (CABs) that includes hyperactive, stereotyped, aggressive, and self‐injurious behaviors. Brain imaging studies have found that several of these individuals have abnormalities in their dopaminergic neurotransmitter systems that are thought to be responsible in part, for the development of these behaviors. The present study evaluated the effects of a selective dopamine re‐uptake blocker, GBR‐12909 in three animal models of varying striatal dopamine concentrations. The three animal models included the neonatal 6‐hydroxydopamine (6‐OHDA)‐lesioned rat, a model of dopamine neuronal depletion, the prenatal methylazoxymethanol (MAM)‐exposed rat, a model of hyper‐dopaminergic innervation and control rats, a model of normal dopaminergic function. The animals were given five daily injections of GBR‐12909 and videotaped observations were conducted immediately following the injections and 6 h later. The results of the study indicate that the MAM‐treated rats exhibited more hyperactive behaviors than either the 6‐OHDA or the control animals in response to the GBR‐12909 injections. However, the 6‐OHDA and control rats exhibited more self‐injurious behaviors than the MAM rats. Interestingly, the topography of the self‐injurious behavior exhibited differed from that we have previously observed in 6‐OHDA lesioned rats following dopamine agonists and resembles the mouthing behaviors seen in some individuals with mental retardation, in particular those with Rett syndrome. These findings indicate the models of varying dopaminergic function interact differently with a dopamine re‐uptake blocker than dopamine agonists and that the partially dopamine depleted model may model the behaviors seen in individuals with Rett syndrome.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0736-5748 1873-474X
DOI:	10.1016/S0736-5748(02)00054-0