Bidirectional actions of docosahexaenoic acid on hippocampal neurotransmissions in vivo.

Docosahexaenoic acid (DHA), a 22-carbon fatty acid with six double bonds, is one of the major polyunsaturated fatty acids in fish oils or in the mammalian central nervous system and is believed to be essential for neuronal plasticity and development. In the present study, we evaluated the effect of DHA on hippocampal neurotransmissions using anesthetized rats. Field excitatory postsynaptic potential (fEPSP) evoked by stimulation of the Schaffer collaterals was recorded from the CA1 stratum radiatum. Following intracerebroventricular injection of DHA 25 nmol, the fEPSP slope decreased gradually in 30 min and was eventually suppressed by about 30%. On the other hand, when fEPSP was evoked by stimulation of the perforant path was recorded in the molecular layer of the dentate gyrus, an increase in fEPSP slope occurred over a similar time course after DHA injection. These phenomena were independent of N-methyl-D-aspartate receptor activity. Linoleic acid, one of polyunsaturated fatty acids, was virtually ineffective. Furthermore, we investigated the effect of DHA on hippocampal synaptic plasticity. Although DHA did not alter the profile of paired-pulse facilitation, it inhibited the induction of long-term potentiation in the CA1 area but not in the dentate gyrus. Thus, DHA exerts regionally different effects on hippocampal neurotransmission and may be a good tool for clarifying physiological functions of the hippocampus.