title: Spatiotemporal alterations of central alpha 1-adrenergic receptor binding sites following amygdaloid kindling seizures in the rat: autoradiographic studies using [3H]prazosin.
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 alpha 1-, alpha 2- and beta 1-adrenergic receptors. In this study, quantitative in vitro autoradiography was used to investigate possible changes in the density of brain alpha 1-adrenergic receptors in a kindling model of epilepsy in the rat. Kindling was produced by daily unilateral stimulation of the amygdala. The alpha 1A+alpha 1B subtypes of adrenergic receptors were labelled with the alpha 1-selective antagonist, [3H]prazosin and alpha 1B receptors, detected in the presence of 10 nM WB4101 to selectively occupy alpha 1A receptors, accounted for 50% of total alpha 1 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 alpha 1A + alpha 1B receptors and alpha 1B 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 alpha 1A + alpha 1B receptors and particularly to alpha 1B receptors in layers I-III of all cortical areas examined. These changes were rapidly induced and the largest increases (range alpha 1A + alpha 1B 80-340%; alpha 1B 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 alpha 1A + alpha 1B and alpha 1B 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 alpha 1A and alpha 1B receptors, or hippocampus which has a low density of both alpha 1 receptor subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Vic., Australia.
authors.forename: A L
authors.initials: AL
authors.lastname: Gundlach
authors.forename: T C
authors.initials: TC
authors.lastname: Burazin
authors.forename: T A
authors.initials: TA
authors.lastname: Jenkins
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000679:Amygdala / Q000502:physiology / Q000503:physiopathology*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D004027:Diencephalon / Q000378:metabolism; D007696:Kindling, Neurologic; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012016:Reference Values; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D011224:Prazosin