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 sei zure development and long-term central nervous system plasticity assoc iated with kindling and epilepsy. These processes involve actions of n oradrenaline at alpha(1)-, alpha(2)-, and beta(1)-adrenergic receptors . In this study, quantitative in vitro autoradiography was used to inv estigate possible changes in the density of brain alpha(1)-adrenergic receptors in a kindling model of epilepsy in the rat. Kindling was pro duced by daily unilateral stimulation of the amygdala. The alpha(1A) alpha(1B) subtypes of adrenergic receptors were labelled with the alph a(1)-selective antagonist, [H-3]prazosin and alpha(1B) receptors, dete cted in the presence of 10 nM WB4101 to selectively occupy alpha(1A) r eceptors, accounted for 50% of total alpha(1) receptors in cerebral co rtex. Autoradiographic studies identified significant and long-lasting , ipsilateral increases in specific [H-3]prazosin binding throughout l ayers I-III of the cortex in sham-operated, unstimulated rats, presuma bly caused by the surgical implantation of the stimulating electrode w ithin the basolateral amygdaloid nucleus. Binding to alpha(1A) +alpha( 1B) receptors and alpha(1B) receptors was increased by an average of 3 5 and 60%, respectively under these conditions. Stimulation-evoked sei zures 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 change s were rapidly induced and the largest increases (range alpha(1A) +alp ha(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, incr eases were measured for both alpha(1A) +alpha(1B) and alpha(1B) recept ors in layers I-III of particular cortical regions, but not overall (e .g. 60-210% increase in perirhinal cortex at both times, with increase s also in retrosplenial, hindlimb, occipital, parietal and temporal co rtices). Between 2-8 wk post-stimulation specific receptor binding lev els were equivalent to those in sham-operated, unstimulated rats. In c ontrast to the large and widespread increases in outer cortical [H-3]p razosin 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 al pha(1B) receptors, or hippocampus which has a low density of both alph a(1) receptor subtypes. Specific changes in alpha(1) receptors reporte d here suggest both a functional involvement of alpha(1) receptor-medi ated mechanisms in the kindling process (i.e, seizure activity and inc reased susceptibility to seizures) and the possible existence of mecha nisms that can enhance the sensitivity of the alpha(1) receptors.