INTRA-CORTICAL SPREAD OF EXOGENOUS CATECHOLAMINES - EFFECTIVE CONCENTRATION FOR MODIFYING CORTICAL PLASTICITY

Abstract

The question of maximal intracortical spread of locally perfused 6-hydroxydopamine (6-OHDA) and norepinephrine (NE) through a continuous microperfusion system was examined in cats. The following analyses were performed: catecholamine (CA) fluorescence histochemistry in 6-OHDA-perfused cortex, spatial distribution of tritium counts in the visual cortex perfused either with [3H]-6-OHDA or with [3H]NE and chemical assay of endogenous CA in 6-OHDA-perfused cortex. High voltage paper electrophoresis was also used to separate unchanged NE from NE metabolites in cortex samples perfused with [3H]NE. The lowest effective concentrations of 6-OHDA for depletion and of NE for restoration of synaptic plasticity in kitten visual cortex were calculated. It was approximately 3 .mu.M for 6-OHDA and 0.3 .mu.M for NE, respectively. This concentration of 6-OHDA seems to be low enough for its specific uptake by CA-containing nerve terminals in the visual cortex. The effective concentration of NE appears to be close to or less than the endogenous level of NE per unit of volume of the normal cortical tissue. By comparing the size of chemical lesions placed by 6-OHDA perfusion in the visual cortex and the spatial distribution of endogenous NE in cortical tissues which had been treated similarly with 6-OHDA, the lower limit of sensitivity of a modified glyoxylic acid-perfusion histofluorescence method for visualizing CA (mostly NE)-containing fibers and terminals was evaluated. The threshold of sensitivity seemed to be 20% of the control.