RT Journal Article SR Electronic T1 Regulation of Septo-Hippocampal Activity by 5-Hydroxytryptamine2C Receptors JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 605 OP 615 DO 10.1124/jpet.103.051169 VO 306 IS 2 A1 Mihály Hajós A1 William E. Hoffmann A1 Royal J. Weaver YR 2003 UL http://jpet.aspetjournals.org/content/306/2/605.abstract AB It is established that the serotonin system modulates hippocampal functions by regulating neuronal activity of both the medial septum and hippocampus. Inhibition of serotonin neurons leads to theta oscillation of septal neurons and theta wave activity in the hippocampus, indicating a tonic regulation of the septo-hippocampal system by serotonin neurons. Because the postsynaptic 5-hydroxytryptamine (5-HT) receptor subtypes mediating this tonic inhibition have not been identified, a putative role of 5-HT2C receptors has been evaluated in the present study. Extracellular single units were recorded from the medial septum/vertical limb of diagonal band (MS/DBv) and hippocampal CA1 or dentate gyrus with simultaneous hippocampal EEG recordings from anesthetized rats. Intravenous administration of 5-HT2C receptor agonists 1-(3-chlorophenyl)piperazine dihydrochloride (m-CPP) and [S]-2-(chloro-5-fluoro-indol-1-yl)-1-methyl-ethylamine fumarate (Ro 60-0175) dose dependently inhibited firing activity most of the recorded MS/DBv neurons and abolished theta oscillation in all tested MS/DBv and hippocampal neurons. Parallel to inhibition of theta oscillation of MS/DBv neurons, hippocampal EEG activity was desynchronized and its power spectrum was shifted to lower frequencies. The selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbomyl] indoline (SB-242084) [but not the 5-HT2B antagonist 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropyl-pyrimidine (RS-127445) or 5-HT2A antagonist R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)-ethyl]-4-piperidinemethanol (MDL-100907)] reversed the action of 5-HT2C receptor agonists. Furthermore, in control rats 5-HT2C receptor antagonists [SB-242084 and 5-methyl-1-(3-pyridil-carbamoyl)-1,2,3,5-tetrahydropyr-rolo[2,3-f]indole hydrochloride (SB-206553)] induced or enhanced theta oscillation in MS/DBv and hippocampal neurons and theta wave activity of the hippocampus. These findings provide evidence for a tonic regulation of the activity and theta oscillation of the septo-hippocampal system via 5-HT2C receptors in the anesthetized rat, indicating that pharmacological interactions with these receptors could modulate various physiological and pathological processes associated with limbic theta activity. The American Society for Pharmacology and Experimental Therapeutics