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

• Published in: Neuropharmacology 2002-01, Vol.42 (1), p.82-92
• Main Authors: Gill, CH, Soffin, E M, Hagan, J J, Davies, CH
• Format: Article
• Language: English
• ISSN: 0028-3908

In the CA3 region of rat hippocampal slices gamma -amino-butyric acid (GABA) sub(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 mu M) and 8-hydroxydipropylaminotetralin (8-OH-DPAT). The selective 5-HT sub(1A) receptor antagonist N-(2-(4-(2-methoxyphenyl)1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclo hexane carboxamide (WAY 100635) reversed the depression of bursting activity whereas the 5-HT sub(7)- receptor antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl) phenol (SB-269970; 1-10 mu M), but not the 5-HT sub(1A). sub(4) or sub(6) receptor antagonists WAY 100635 (10 mu M), SB-204070 (10 mu M) and SB-271046 (l0 mu M), reversed the increase in bursting activity. The apparent log sub(10) K sub(D) value (8.4) for the effect of SB-269970 was consistent with a selective action at 5-HT sub(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 sub(7) receptor-mediated inhibition of a Ca super(2+) activated K super(+) channel.