Branched-chain amino acid-induced hippocampal norepinephrine release is antagonized by picrotoxin: evidence for a central mode of action

Abstract Previous studies indicated that administration of a 1:1:1 mixture of the branched-chain amino acids leucine, isoleucine, and valine (BCAA) decreased the response to pain. The present study investigates the effects of BCAA on release of norepinephrine (NE) from isolated hippocampal brain slices. BCAA evoked 3 H-NE release in a concentration-dependent manner. This effect was antagonized by the gamma aminobutyric acid (GABA) receptor antagonist picrotoxin, again in a concentration-dependent manner, suggesting that the effect may be mediated via a GABA receptor. Given the role of NE and of GABA receptors in the central response to pain, it is possible that the BCAA may exert their antinociceptive properties through activation of GABA receptors.