NEONATAL DESTRUCTION OF DOPAMINERGIC-NEURONS

Rats treated as neonates with 6-hydroxydopamine are proposed to model the dopamine deficiency associated with Lesch-Nyhan syndrome (LNS). To understand the neurobiological basis of specific behaviors in LNS, in vestigations were undertaken in these neonatally lesioned rats. Severa l new findings resulted from these studies. The first was that D1-dopa mine receptors are essential for the action of D2-dopamine receptors, a phenomenon called ''coupling'' of receptor function. Another finding was that D1-dopamine receptors must be repeatedly stimulated before m aximal behavioral sensitivity can be observed. This has been referred to as ''priming'' of D1-dopamine receptor responsiveness. This priming action by repeated administration of a D1-dopamine agonist was antago nized by NMDA antagonists indicating a potential role of glutamate in this sensitization. Ongoing work suggests that DARPP-32 is not involve d in priming of D1-dopamine receptor responsiveness. However, we have observed an accumulation of GFAP in brain following repeated administr ation of a D1-dopamine agonist. In addition, immunoblots employing an antibody to phospho-DARPP-32 revealed a protein present in lesioned ra t that was not present in control rats. Studies in these lesioned rats are expected to continue to contribute to our basic understanding of adaptive changes caused by lesioning of dopaminergic neurons during de velopment. (C) 1994 Infox Press, Inc.