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 from the use of the neurotoxin 2,4,5-trihydroxyphenylethylamine, or 6-hydroxydopamine (6-OHDA), that destroys catecholamine-containing neuronal cell bodies and nerve terminals. Refinements in the use of this neurotoxin led to the use of dopamine-denervated animals as models of human Parkinson's disease, in which the loss of dopaminergic neurons is a prominent feature. Here we review structural, pharmacological, and biochemical studies carried out in the adult and neonatal 6-OHDA lesioned animals. These models have become useful and interesting paradigms to examine alterations in the expression of receptors and in their sensitivity to agonist drugs; some of these modifications may underlie the altered responsiveness of the dopamine-lesioned animals to dopamine, but also to other compounds, including serotoninergic drugs. We have also reviewed studies of amino acids as well as of monoamine metabolism and of uptake mechanisms that may underlie some of the behavioural alterations in these models that have become relevant for our understanding of the sprouting and plastic properties of spared neurons, and of the alternate neuronal projections that replace lesioned terminals, enabling compensatory adaptations. Although 6-OHDA-lesioned animals, that display some biochemical characteristics of Parkinson's disease in humans, do not express all of the neurological features exhibited by patients, the increasing knowledge that can be obtained from studies in simplified experimental models will undoubtedly lead to the development of innovative drugs and other replacement therapies for degenerative brain diseases.
Reader
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TA
Département de Physiologie, Faculté de Médecine, Université de Montréal, Québec, Canada. readert@ere.umontreal.ca
Dewar
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KM
D000818:Animals; D000831:Animals, Newborn; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D017072:Neostriatum / Q000503:physiopathology*; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000503:physiopathology*; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine