5-HT 7 receptors modulate synchronized network activity in rat hippocampus

Abstract

In the CA3 region of rat hippocampal slices γ-amino-butyric acid (GABA) A/B receptor antagonists induce low frequency bursting activity that was either inhibited (in 21% of slices) or increased by the selective 5-HT receptor agonists 5-carboxy-tryptamine (0.1–1 μM) and 8-hydroxydipropylaminotetralin (8-OH-DPAT). The selective 5-HT 1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide (WAY 100635) reversed the depression of bursting activity whereas the 5-HT 7 receptor antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970; 1–10 μM), but not the 5-HT 1A, 4 or 6 receptor antagonists WAY100635 (10 μM), SB-204070 (10 μM) and SB-271046 (10 μM), reversed the increase in bursting activity. The apparent −log 10 K D value (8.4) for the effect of SB-269970 was consistent with a selective action at 5-HT 7 receptors. Accompanying the 5-CT-induced increase in bursting frequency there was a shortening of the burst event waveform and a reduction in the after-hyperpolarization following each bursting event both of which were inhibited by SB-269970. These effects appeared to result predominantly from a direct 5-HT 7 receptor-mediated inhibition of a Ca 2+ activated K + channel.