The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles
- 作者：Breese ; George R. ; Knapp ; Darin J. ; Criswell ; Hugh E. ; Moy ; Sheryl S. ; Papadeas ; Sophia T. ; et. al.
- 关键词：Neural basis of behavior ; Neural plasticity ; Neonate dopamine lesion ; 6-Hydroxydopamine ; Self-injurious behavior ; NMDA hypofunction ; Behavioral sensitization ; Serotonin hyperinnervation ; D1-dopamine receptors ; NMDA receptor antagonists
- 刊名：Brain Research Reviews
- 出版年：2005
- 期刊代码：11_01650173
- 类别：neu
- 出版时间：February, 2005
- 卷：48
- 期：1
- 页码：57-73
- 文件大小：476 K
摘要
In 1973, a technique of administering 6-hydroxydopamine (2,4,5-trihydroxyphenylethylamine) intracisternally to neonate rats was introduced to selectively reduce brain dopamine (neonate-lesioned rat). This neonate treatment proved unique when compared to rats lesioned as adults with 6-hydroxydopamine芒芒芒prompting the discovery of differing functional characteristics resulting from the age at which brain dopamine is reduced. A realization was that neonate-lesioned rats modeled the loss of central dopamine and the increased susceptibility for self-injury in Lesch芒芒芒Nyhan disease, which allowed identification of drugs useful in treating self-injury in mentally retarded patients. The neonate-lesioned rat has also been proposed to model the hyperactivity observed in attention-deficit hyperactivity disorder. Because the neonate-lesioned rat exhibits enhanced sensitization to repeated NMDA receptor antagonist administration and has functional changes characteristic of schizophrenia, the neonate lesioning is believed to emulate the hypothesized NMDA hypofunction in this psychiatric disorder. Besides modeling features of neurological and psychiatric disorders, important neurobiological concepts emerged from pharmacological studies in the neonate-lesioned rats. One was the discovery of coupling of D1/D2-dopamine receptor function. Another was the progressive increase in responsiveness to repeated D1-dopamine agonist administration referred to as 芒芒芒priming芒芒芒 of D1-dopamine receptor function. Additionally, a unique profile of signaling protein expression related to neonate reduction of dopamine has been identified. Thus, from modeling characteristics of disease to defining adaptive mechanisms related to neonatal loss of dopamine, the neonate-lesioned rat has had a persisting influence on neuroscience. Despite an extraordinary legacy from studies of the neurobiology of this treatment, a host of unknowns remain that will inspire future investigations.