EXCITATORY ACTIONS OF DEHYDROABIETIC ACID ON MAMMALIAN SYNAPTOSOMES

The presynaptic effects of dehydroabietic acid were investigated using mouse brain synaptosomes as the in vitro model. At concentrations ran ging from 10 to 100 mu M, dehydroabietic acid depolarises the synaptos omal membrane and causes pronounced release of the neurotransmitters g amma-aminobutyric acid, acetylcholine and L-glutamate. The effects on membrane potential and transmitter release occur predominantly at conc entrations below which any lytic actions of this compound can be detec ted. Dehydroabietic acid-induced depolarisation and release of neurotr ansmitters are not influenced by tetrodotoxin and are associated with only marginal inhibition of membrane-associated ATPase activity. When synaptosomes are challenged with dehydroabietic acid in calcium-free s aline, a partial reduction in the stimulated release of transmitters i s observed. These results provide dear evidence that dehydroabietic ac id is neuroactive and capable of causing substantial increases in the release of both excitatory and inhibitory neurotransmitter substances. The mechanism which underlies the neuroexcitatory effects of dehydroa bietic acid remains to be resolved however it is proposed that release of transmitters from central nerve endings may be a contributory fact or in the toxicity of resin acids.