Elsevier

Brain Research

Volume 672, Issues 1–2, 20 February 1995, Pages 214-227
Brain Research

Research report
Spatiotemporal alterations of central α1-adrenergic receptor binding sites following amygdaloid kindling seizures in the rat: autoradiographic studies using [3H]prazosin

https://doi.org/10.1016/0006-8993(94)01338-IGet rights and content

Abstract

Noradrenergic neurons are thought to be involved in the process of seizure development and long-term central nervous system plasticity associated with kindling and epilepsy. These processes involve actions of noradrenaline at α1-, α2- and β1-adrenergic receptors. In this study, quantitative in vitro autoradiography was used to investigate possible changes in the density of brain α1-adrenergic receptors in a kindling model of epilepsy in the rat. Kindling was produced by daily unilateral stimulation of the amygdala. The α1A + α1B subtypes of adrenergic receptors were labelled with the α1-selective antagonist, [3H]prazosin and α1B receptors, detected in the presence of 10 nM WB4101 to selectively occupy α1A receptors, accounted for 50% of total α1 receptors in cerebral cortex. Autoradiographic studies identified significant and long-lasting, ipsilateral increases in specific [3H]prazosin binding throughout layers I–III of the cortex in sham-operated, unstimulated rats, presumably caused by the surgical implantation of the stimulating electrode within the basolateral amygdaloid nucleus. Binding to α1A + α1B receptors and α1B receptors was increased by an average of 35 and 60%, respectively under these conditions. Stimulation-evoked seizures produced dramatic bilateral increases in specific [3H]prazosin binding to α1A + α1B receptors and particularly to α1B receptors in layers I–III of all cortical areas examined. These changes were rapidly induced and the largest increases (range α1A + α1B 80–340%; α1B 165–380%) occurred at 0.5–2 h after the last stage 5 kindled seizure. At 1 and 3 days after the last seizure, increases were measured for both α1A + α1B receptors in layers I–III of particular cortical regions, but not overall (e.g. 60–210% increase in perirhinal cortex at both times, with increases also in retrosplenial, hindlimb, occipital, parietal and temporal cortices). Between 2–8 wk post-stimulation specific receptor binding levels were equivalent to those in sham-operated, unstimulated rats. In contrast to the large and widespread increases in outer cortical [3H]prazosin binding, smaller increases were detected in the inner cortex (layer V–VI) at individual times (65–75% increase at 30 min), while no significant changes occurred in several other brain regions examined, including thalamus, which contained a high density of α1A and α1B receptors, or hippocampus which has a low density of both α1 receptor subtypes. Specific changes in α1 receptors reported here suggest both a functional involvement of α1 receptor-mediated mechanisms in the kindling process (i.e. seizure activity and increased susceptibility to seizures) and the possible existence of mechanisms that can enhance the sensitivity of the α1 receptors.

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