Exofocal Alterations in Opioidergic Receptor Densities Following Focal Cerebral Ischemia in the Mouse

• Published in: Experimental neurology 2000-08, Vol.164 (2), p.314-321
• Main Authors: Boutin, Hervé, Dauphin, François, Jauzac, Philippe, MacKenzie, Eric T.
• Format: Article
• Language: English
• Subjects: [3H]DADLE; [3H]DAMGO; [3H]diprenorphine; [3H]U69,593; Analysis of Variance; Animals; Autoradiography; Binding Sites; Biological and medical sciences; Brain - cytology; Brain - metabolism; Brain - pathology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Corpus Striatum - cytology; Corpus Striatum - metabolism; Infarction, Middle Cerebral Artery; Ligands; Medical sciences; Mice; Neurology; Receptors, Opioid, delta - metabolism; Receptors, Opioid, kappa - metabolism; Receptors, Opioid, mu - metabolism; striatum; Substantia Nigra - cytology; Substantia Nigra - metabolism; Thalamic Nuclei - cytology; Thalamic Nuclei - metabolism; thalamus; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7400

In previous studies of our group, we have reported differential alterations in opioidergic receptor subtypes densities in infarcted and periinfarcted brain tissue following middle cerebral artery occlusion (MCAO) in mice. Other studies have also described subcortical alterations consecutive to focal cortical ischemia. For a better understanding of ischemic processes in exofocal areas, we have investigated the evolution of opioidergic receptors following focal cortical ischemia through the quantification of relative binding densities, Bmax and Kd values for the μ, δ, and κ subtypes. Our results demonstrate that opioid receptor subtypes exhibit adaptations at distance from the ischemic core, mainly in the striatum, the thalamus, and the substantia nigra. Indeed, μ and δ Bmax values were increased in ventral thalamic nuclei, while κ relative binding densities were transiently increased in nucleus medialis dorsalis and nucleus lateralis, pars posterior. Moreover, the Bmax of μ and δ receptors were transiently decreased at 6 h post-MCAO in ipsi- and contralateral patches and matrices of the striatum. Conversely, the μ Bmax values were increased in ipsi- and contralateral substantia nigra, pars compacta, and pars reticulata, 24 h following MCAO. In contralateral substantia nigra, pars compacta, κ Bmax was found to be decreased at 24 h post-MCAO. These alterations could reflect neuronal dysfunction in exofocal brain structures, consecutively to the degeneration of defined neuroanatomical pathways. Our study indicates that opioidergic receptors could be used as markers of the neuronal reorganization that take place in subcortical areas following an ischemic insult of the brain cortex.