In vivo neurotransmitter release in the locus coeruleus--effects of hyperforin, inescapable shock and fear.

Abstract

Hyperforin, the main antidepressant constituent of Hypericum perforatum, influences the extracellular concentrations of transmitters in vitro and in vivo. In vivo experiments have shown that hyperforin enhances the extracellular concentrations of dopamine, norepinephrine, serotonin and glutamate in the locus coeruleus. Hyperforin-free Hypericum extract also elevates the extracellular concentrations of dopamine and norepinephrine in the locus coeruleus, but, in contrast to hyperforin, the extracellular concentration of serotonin is diminished. The differing profiles of hyperforin and hyperforin-free Hypericum extract on the extracellular transmitter concentrations point to the presence of an additional biologically active compound in Hypericum perforatum. Inescapable shock increases the release of monoamines and several amino acids, as well as motility, blood pressure and heart rate. Conditioned fear, similar to hyperforin-free Hypericum extract, decreases the release of serotonin in the locus coeruleus. Conditioned fear also leads to tachycardia. The latter finding shows that telemetric heart rate recording is a good index for conditioned fear. In vivo findings confirm the idea that the anti-depressive properties of Hypericum extract and hyperforin result from increases in extracellular neurotransmitter concentrations. Since hyperforin-free extract, like conditioned fear, reduces the extracellular concentration of serotonin, hyperforin may be more beneficial than Hypericum extract in the treatment of depressive disorders.