Effects of denervation and hyperinnervation on dopamine and serotonin systems in the rat neostriatum: implications for human Parkinson's disease

The research on central synaptic neurotransmission has greatly benefited fr om the use of the neurotoxin 2,4,5-trihydroxyphenylethylamine, or 6-hydroxy dopamine (6-OHDA), that destroys catecholamine-containing neuronal cell bod ies and nerve terminals. Refinements in the use of this neurotoxin led to t he use of dopamine-denervated animals as models of human Parkinson's diseas e, in which the loss of dopaminergic neurons is a prominent feature. Here w e review structural, pharmacological, and biochemical studies carried out i n the adult and neonatal 6-OHDA lesioned animals. These models have become useful and interesting paradigms to examine alterations in the expression o f receptors and in their sensitivity to agonist drugs; some of these modifi cations may underlie the altered responsiveness of the dopamine-lesioned an imals to dopamine, but also to other compounds, including serotoninergic dr ugs. We have also reviewed studies of amino acids as well as of monoamine m etabolism and of uptake mechanisms that may underlie some of the behavioura l alterations in these models that have become relevant for our understandi ng of the sprouting and plastic properties of spared neurons, and of the al ternate neuronal projections that replace lesioned terminals, enabling comp ensatory adaptations. Although 6-OHDA-lesioned animals, that display some b iochemical characteristics of Parkinson's disease in humans, do not express all of the neurological features exhibited by patients, the increasing kno wledge that can be obtained from studies in simplified experimental models will undoubtedly lead to the development of innovative drugs and other repl acement therapies for degenerative brain diseases. (C) 1999 Elsevier Scienc e Ltd. All rights reserved.