Serotonin inhibits the depolarization-evoked release of endogenous glutamate from rat cerebellar nerve endings.

Glutamic acid (Glu) has been proposed as the neurotransmitter of cerebellar granule cells. 5-Hydroxytryptamine (5-HT) afferents project to the cerebellar cortex. The possible interaction between 5-HT and Glu was investigated by studying the effect of 5-HT on Glu release. The Ca2+-dependent depolarization-evoked release of endogenous Glu from superfused rat cerebellar synaptosomes was potently inhibited by 5-HT. Methiothepin, but not ketanserin, cinanserin or methysergide, antagonized 5-HT. It is concluded that the release of Glu can be modulated by 5-HT through receptors sited on Glu terminals. These receptors belong to the 5-HT1-type.