Motor activity and gene expression in rats with neonatal 6‐hydroxydopamine lesions
- 6 September 2004
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 91 (1), 9-19
- https://doi.org/10.1111/j.1471-4159.2004.02615.x
Abstract
A rat model of a hyperkinetic disorder was used to investigate the mechanisms underlying motor hyperactivity. Rats received an intracisternal injection of 6-hydroxydopamine on post-natal day 5. At 4 weeks of age, the animals showed significant motor hyperactivity during the dark phase, which was attenuated by methamphetamine injection. Gene expression profiling was carried out in the striatum and midbrain using a DNA macroarray. In the striatum at 4 weeks, there was increased gene expression of the NMDA receptor 1 and tachykinins, and decreased expression of a GABA transporter. At 8 weeks, expression of the NMDA receptor 1 in the striatum was attenuated, with enhanced expression of the glial glutamate/aspartate transporter. In the midbrain, a number of genes, including the GABA transporter gene, showed decreased expression at 4 weeks. At 8 weeks, gene expression was augmented for the dopamine transporter, D4 receptor, and several genes encoding peptides, such as tachykinins and their receptors. These results suggest that in the striatum the neurotransmitters glutamate, GABA and tachykinin may play crucial roles in motor hyperactivity during the juvenile period. Several classes of neurotransmitters, including dopamine and peptides, may be involved in compensatory mechanisms during early adulthood. These data may prompt further neurochemical investigations in hyperkinetic disorders.Keywords
This publication has 51 references indexed in Scilit:
- Neuropeptides and social behavior: animal models relevant to autismMolecular Psychiatry, 2002
- Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: Therapeutic implicationsSynapse, 2001
- Binding of Factor VIIa to Tissue Factor on Keratinocytes Induces Gene ExpressionPublished by Elsevier BV ,2000
- Progressive Augmentation of Striatal and Accumbal Preprotachykinin mRNA Levels by Chronic Treatment with Methamphetamine and Effect of Concurrent Administration of the N-methyl-d-aspartate Receptor Antagonist MK-801Neuropharmacology, 1997
- NMDA-NR1 receptor subunit mRNA expression in rat brain after 6-OH-dopamine induced lesions: A non-isotopic in situ hybridization studyJournal of Neuroscience Research, 1996
- Blockade of Prefronto‐cortical α1‐Adrenergic Receptors Prevents Locomotor Hyperactivity Induced by Subcortical D‐Amphetamine InjectionEuropean Journal of Neuroscience, 1994
- Localization of neurokinin B in the central nervous system of the ratPeptides, 1992
- Neonatal and Adult 6‐Hydroxydopamine‐Induced Lesions Differentially Alter Tachykinin and Enkephalin Gene ExpressionJournal of Neurochemistry, 1987
- Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamineNature, 1976
- Selective Brain Dopamine Depletion in Developing Rats: An Experimental Model of Minimal Brain DysfunctionScience, 1976