We have examined the astrocytic involvement in and developmental profile of a transient heterosynaptic depression (tHeSD) in the CA1 region of the rat hippocampal slice preparation. A short stimulus burst (3 impulses at 50 Hz) to one group of synapses elicited a depression of the field EPSP evoked in another group of synapses that amounted to about 25 % 0.5 s after the conditioning burst. This tHeSD was associated with an increase in the paired-pulse ratio of about 30 %. The tHeSD was not present in slices from rats younger than ten postnatal days and developed towards the adult magnitude between postnatal days ten and twenty. The tHeSD was totally prevented by fluoroacetate, an astrocytic metabolic inhibitor. In addition, carbenoxolone, a general blocker of connexin- based channels inhibited the tHeSD as well as endothelin, an endogenous peptide that has been shown to block astrocytic connexin-based channels. Antagonists to GABA^B - and group II/III metabotropic glutamate receptors abolished the tHeSD whereas antagonists to NMDA- , adenosine 1- and group I metabotropic glutamate receptors did not affect the tHeSD. These results suggest that tHeSD relies on GABA^B receptors, group II/III metabotropic glutamate receptors and on gliotransmitter release from astrocytes.