The effects of footshock and handling on tyrosine hydroxylase activity in synaptosomes and solubilised preparations from rat brain.

The effects of mild noxious stimulation on central noradrenergic activity were investigated in rats, using low-intensity electrical footshock as the noxious stimulus. Synaptosomes were prepared from brain regions of control and experimental rats and the rate of tyrosine hydroxylation was assayed: this is a measure of transmitter synthesis in the isolated noradrenergic terminals. Single footshocks were found to elevate the synthesis rate in the hippocampus, the extent of the elevation depending on the baseline rate. This elevation was not significant in hypothalamus or cerebellum. Repeated handling over a period of 14 days was also found to elevate synthesis rate in hippocampus; but rats subjected to daily footshock for a week, in addition to handling, had synthesis rates similar to those of controls. Maximal tyrosine hydroxylase activity was measured by solubilizing the enzyme and assaying at saturating concentrations of cofactor and substrate: this is a measure of the amount of enzyme in the nerve terminals. No significant changes in maximal tyrosine hydroxylase activity were found in the brains of handled or shocked animals. These results suggest that the assay of tyrosine hydroxylase activity in a suspension of synaptosomes provides a sensitive indicator of changes in noradrenergic activity related to mild noxious stimulation. The biochemical responses are more pronounced in the hippocampus than in other noradrenergic terminal areas; this suggests that the synthesis rate of noradrenaline in terminals of central noradrenergic neurones could be regulated by local mechanisms at the terminal as well as by impulses transmitted from the cell body.