EFFECT OF INJURY ON THE BI-AFFINITY ALPHA(1)-ADRENOCEPTOR BINDING IN RAT-BRAIN IN-VIVO

Focal freezing lesions in rats cause a widespread decrease of cortical glucose utilization in the lesioned hemisphere, probably as a reflect ion of depressed cortical activity. The noradrenergic neurotransmitter system was implicated in these alterations when it was demonstrated t hat prazosin, a specific norepinephrine (NE) antagonist at alpha(1)-ad renergic receptors, prevented their development, In normal rat brain, specific binding of [I-125]HEAT odo-4-hydroxyphenyl)-ethyl-aminomethyl -tetralone], another selective alpha(1)-adrenoreceptor ligand, was dem onstrated in vivo at sites consistent with the alpha(1A)- and alpha(1B )-adrenoreceptor subtypes, In the present study, the effect of a freez ing lesion on specific binding of [I-125]HEAT in rat brain in vivo was determined three days after traumatization when cortical glucose use suggested the greatest degree of functional depression. The steady-sta te volumes of distribution of [I-125]HEAT three days after injury were significantly increased in all the cortical areas of the lesioned hem isphere, but not in the subcortical structures. Injury did not modify the binding affinities for HEAT. However, a statistically significant increase in the number of low-affinity binding sites for this ligand w as demonstrated in all cortical areas of the lesioned hemisphere, but not in subcortical structures. The traumatization did not modify B-max estimates for the high-affinity binding of HEAT. The results support the hypothesis that changes in the noradrenergic system are of functio nal importance in brain injury and that at least some effects of injur y are mediated by alpha(1B)-adrenergic receptors. (C) 1995 Wiley-Liss, Inc.