Intracortical spread of exogenous catecholamines: effective concentration for modifying cortical plasticity.

The present study is aimed to clarify the question of maximal intracortical spread of locally perfused 6-hydroxydopamine (6-OHDA) and norepinephrine (NE) through a continuous microperfusion system. The following analyses were performed: 1) catecholamine (CA) fluorescence histochemistry in 6-OHDA-perfused cortex, 2) spatial distribution of tritium counts in the visual cortex perfused either with [3H]-6-OHDA or with [3H]N# and 3) chemical assay of endogenous CAs in 6-OHDA-perfused cortex. 4) High voltage paper electrophoresis was also used to separate unchanged NE from NE metabolites in cortex samples perfused with [3H]NE. Taking the present results together with those in previous physiological assays of cortical synaptic plasticity, we calculated the lowest effective concentration of 6-OHDA for depletion and of NE for restoration of synaptic plasticity in kitten visual cortex: it was approximately 3 microM for 6-OHDA and 0.3 microM 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. In addition, 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, we evaluated the lower limit of sensitivity of a modified glyoxylic acid-perfusion histofluorescence method for visualizing CA (mostly NE)-containing fibers and terminals. The threshold of sensitivity seemed to be 20% of the control.