Pharmacological characterization of 5‐HT1B receptor‐mediated inhibition of local excitatory synaptic transmission in the CA1 region of rat hippocampus

• Published in: British journal of pharmacology 2003-01, Vol.138 (1), p.71-80
• Main Authors: Mlinar, Boris, Falsini, Chiara, Corradetti, Renato
• Format: Article
• Language: English
• Subjects: 5‐HT; 5‐HT1B receptor; Biological and medical sciences; CA1; Cell receptors; Cell structures and functions; CGS 12066B; CP 93129; Electrophysiology; epsc; Fundamental and applied biological sciences. Psychology; GR 55562; hippocampus; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); presynaptic inhibition
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705026

In the hippocampus, axon collaterals of CA1 pyramidal cells project locally onto neighbouring CA1 pyramidal cells and interneurones, forming a local excitatory network which, in disinhibited conditions, feeds polysynaptic epscs (poly‐epscs). 5‐hydroxytryptamine (5‐HT) has been shown to inhibit poly‐epscs through activation of a presynaptic receptor. The aim of the present work was the pharmacological characterization of the 5‐HT receptor involved in this 5‐HT action. Poly‐epscs, evoked by electrical stimulation of the stratum radiatum and recorded in whole‐cell voltage‐clamp from CA1 pyramidal neurones, were studied in mini‐slices of the CA1 region under pharmacological block of GABAA, GABAB, and 5‐HT1A receptors. The 5‐HT1B receptor selective agonist 1,4‐dihydro‐3‐(1,2,3,6‐tetrahydro‐4‐pyridinyl)‐5H‐pyrrolo[3,2‐b]pyridin‐5‐one dihydrochloride (CP 93129) inhibited poly‐epscs (EC50=55 nM), an effect mimicked by the 5‐HT1B ligands 5‐carboxamidotryptamine (5‐CT; EC50=14 nM) and methylergometrine (EC50=78 nM), but not by 1‐(3‐chlorophenyl)piperazine dihydrochloride (mCPP; 10 μM) or 7‐trifluoromethyl‐4(4‐methyl‐1‐piperazinyl)‐pyrrolo[1,2‐a]quinoxaline dimaleate (CGS 12066B; 10 μM). The effects of CP 93129 and 5‐CT were blocked by the selective 5‐HT1B receptor antagonist 3‐[3‐(dimethylamino)propyl]‐4‐hydroxy‐N‐[4‐(4‐pyridinyl)phenyl]benzamide dihydrochloride (GR 55562; KB∼100 nM) and by cyanopindolol (KB=6 nM); methiothepin (10 μM) and dihydroergotamine (1 μM). For both GR 55562 and methiothepin, application times of at least two hours were required in order to achieve their full antagonistic effects. Our results demonstrate that 5‐HT1B receptors are responsible for the presynaptic inhibition of neurotransmission at CA1/CA1 local excitatory synapses exerted by 5‐HT. British Journal of Pharmacology (2003) 138, 71–80. doi:10.1038/sj.bjp.0705026