Endogenous 5-HT Tonically Inhibits Spontaneous Firing Activity of Dorsal Hippocampus CA1 Pyramidal Neurons Through Stimulation of 5-HT1A Receptors in Quiet Awake Rats In Vivo Electrophysiological Evidence

Abstract

The present study was performed to examine an overall effect of endogenous serotonin (5-HT) on the spontaneous firing activity of the dorsal hippocampus CA1 pyramidal neurons in quiet awake rats. A selective 5-HT 1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY-100635: 0.03-0.2 mg/kg, s.c.) It has been shown that there are at least 14 serotonin (5-HT; 5-hydroxytryptamine) receptor subtypes over seven distinct receptor subfamilies. Among these seven receptor subfamilies, only the 5-HT 1 subfamily is inhibitory whereas the others are excitatory (see Hoyer et al. 1994; Glennon and Dukat 1995 for reviews). Several in situ hybridization studies have demonstrated that ten of these 14 receptor subtypes are detectable over the CA1 region of the rat hippocampus (see Andrade 1998 for review).In accordance with the distribution and exuberance of 5-HT receptors expressed in this area, several in vitro electrophysiological studies have demonstrated multiple actions of 5-HT on the excitability of the CA1 pyramidal neurons. These are the direct inhibitory and exci- 142 K. Kasamo et al. N EUROPSYCHOPHARMACOLOGY 2001 -VOL . 24 , NO . 2 tatory actions through stimulating 5-HT 1A and 5-HT 4 receptors on the pyramidal neurons, respectively. In addition, via inhibitory interneurons, 5-HT indirectly decreases and increases the excitability through stimulating 5-HT 2 and 5-HT 3 , and 5-HT 1A receptors, respectively (see Hoyer et al. 1994; Aghajanian 1995; Andrade 1998 for reviews). Given these extremely diverse actions of 5-HT demonstrated in vitro , endogenous 5-HT should produce multiple actions simultaneously on the excitability of the CA1 pyramidal neurons in vivo. These in vitro data have been obtained with the preparations isolated from various potentially confounding factors, such as the effects of activation of other receptor systems. Contrary, in vivo cells in the brain are exposed continuously to the various neurotransmitter, neuromodulator and hormonal stimuli. In any cell, these stimuli are integrated spatially and temporally. Furthermore, the intracellular signaling cascades are extensively interconnected. Moreover, even in vivo , the use of anesthesia drastically reduces the 5-HT tone (Jacobs 1985; as well as the spontaneous firing activity of the hippocampus pyramidal neurons (Blier et al. 1993). The reduction in the firing activity indicates that the use of anesthesia per se markedly decreases the excitability of hippocampal pyramidal neurons. Thus, an overall action of endogenous 5-HT on the firing activity of the pyramidal neurons in awake rats is unpredictable solely basing on the data obtained from in vivo studies with anesthetized animals and from in vitro experiments. Therefore, using awake animals is essential to scrutinize the influence of endogenous 5-HT. To our knowledge, such studies examining the net effect of endogenous 5-HT on cellular activity in the brain of awake rats have not been performed so far.Thus, the present study was carried out to...

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