SPATIOTEMPORAL ALTERATIONS OF CENTRAL ALPHA(1)-ADRENERGIC RECEPTOR-BINDING SITES FOLLOWING AMYGDALOID KINDLING SEIZURES IN THE RAT - AUTORADIOGRAPHIC STUDIES USING [H-3] PRAZOSIN

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, [H-3]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 [H-3]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 [H-3]prazosin binding to alpha(1A) +alpha(1B)eceptors 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 [H-3]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. Specific changes in alpha(1) receptors reported here suggest both a functional involvement of alpha(1) 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 alpha(1) receptors.