PSYCHOPHARMACOLOGY OF DOPAMINE ONTOGENY

这一奖项的申请概述了一系列的细胞外

This First Award application outlines a series of extracellular electrophysiological studies designed to provide new preclinical information concerning the physiology and pharmacology of mesencephalic dopamine (DA)-containing neurons during development. The anatomy, physiology, biochemistry and pharmacology of dopamine-containing neurons have been extensively studied over the past several decades. The electrophysiological characteristics and neuropharmacology of single identified adult mammalian DA neurons have been reported by many investigators. DA neurons undergo rapid and dramatic morphological and functional changes during prenatal and postnatal ontogeny. Although most of the monoamine-containing neurons and their axonal pathways are well developed at birth, much of the synaptogenesis occurs during postnatal development. Very little is known about the electrophysiological characteristics and neuropharmacology of single identified mammalian DA neurons during the postnatal developmental period. Experiments are proposed within this application which are directed towards elucidating some of the basic physiological and pharmacological properties of antidromically identified DA neuron subpopulations. The physiology and pharmacology of antidromically identified nigrostriatal (NSDA) and mesoaccumbens (MADA) DA neurons will be examined and compared during postnatal development in the rat (1-day-old to 5-weeks-old) using single-unit extracellular electrophysiological techniques. The physiological properties of developing NSDA and MADA neurons to be examined include basal discharge rate, discharge pattern (e.g., burst activity) and conduction velocity. The postnatal development of somato- dendritic and terminal DA autoreceptors in NSDA and MADA neurons will be examined and compared using both systemically and iontophoretically applied DA agonists and antagonists. Monoamine neurotransmitters are known to appear in the central nervous system during very early prenatal ontogeny. A number of investigators have proposed that monoamine neurotransmitters, such as dopamine and serotonin, may have trophic functions in the developing CNS. Experiments within this proposal are designed to examine the prenatal and postnatal influence of serotonergic afferents on the physiological and pharmacological development of NSDA neurons. These proposed studies will provide new critical data on the postnatal developmental stages which mark the progression to normally functioning adult DA neurons and will be relevant to our understanding of psychiatric disorders.