Effects of several 5-HT1A agonists on hippocampal rhythmical slow activity in unanesthetized rats

Kasamo, Kimihiro; Tada, Koji; Kojima, Tetsuhito; Kogure, Miki; Ito, Koichi

doi:10.1016/0028-3908(94)90189-9

Cited by 6 publications

(5 citation statements)

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“…The suppressant effect of buspirone was antagonized by a 5-HT "A antagonist NAN-190 (Claustre et al, 1991) and was unaffected by a selective depletion of endogenous 5-HT in this previous study (Tada et al, 1999). Moreover, the rank order of potency of the 5-HT "A agonists in the suppressant effect agreed with the order at postsynaptic 5-HT "A receptors previously determined in behavioural, electrophysiological and biochemical studies (Bockaert et al, 1987 ;Hadrava et al, 1995 ;Kasamo et al, 1994 ;Millan et al, 1992 ;Sprouse and Aghajanian, 1988). Thus, it has been concluded that systemically administered 5-HT "A agonists suppress the firing activities of CA1 pyramidal neurons by stimulating postsynaptic 5-HT "A receptors in awake rats (Tada et al, 1999).…”

Section: Introductionsupporting

confidence: 85%

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Effects of a benzodioxan derivative MKC-242 on the firing activity of the dorsal hippocampus CA1 pyramidal neurons in awake and urethane- anaesthetized rats: in vivo electrophysiological evidence for a 5-HT 1A agonistic property

Kasamo¹,

Suzuki²,

Tada³

et al. 2000

Int. J. Neuropsychopharm.

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The aim of the present in vivo study was to determine whether a benzodioxan derivative MKC-242, (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole hydrochloride, possesses an agonistic activity at postsynaptic serotonin (5-HT)1A receptors in the rat hippocampus when administered systemically. We examined the effects of acute administrations of MKC-242 on the firing activities of dorsal hippocampus CA1 pyramidal neurons. In quiet awake rats, s.c. administrations of MKC-242 significantly decreased the spontaneous firing activity in a dose-dependent manner at doses of 0.3-6 mg/kg. In urethane-anaesthetized rats, i.v. injections of MKC-242, at cumulative doses of 0.3-3 mg/kg, also significantly and dose-dependently inhibited the firing activity induced by microiontophoretically applied quisqualate. These decreasing effects were antagonized by the selective 5-HT1A antagonists WAY-100135 (5 mg/kg, s.c.) and WAY-100635 (0.2 mg/kg, s.c. to the awake rats and 0.4 mg/kg, i.v. to the anaesthetized rats), thereby confirming that MKC- 242 decreased the firing activities by stimulating 5-HT1A receptors. The selective depletion of 5-HT produced by the 3-d administration of the 5-HT synthesis inhibitor, parachlorophenylalanine (500 mg/kg.d, i.p.), did not affect the decreasing effect of MKC-242 in the awake animals, indicating that postsynaptic 5-HT1A receptors mediated the decreasing effect. The present results provided the first in vivo electrophysiological evidence that MKC-242, when systemically administered, exerts a 5-HT1A agonistic action at the postsynaptic level.

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Section: Introductionsupporting

confidence: 85%

“…Previously, we demonstrated that a 3-d treatment with PCPA (500 mg\kg;d, i.p.) selectively depletes 5-HT in the rat hippocampus to less than 5 % of the control (Kasamo et al, 1994). In the present experiments, such selective depletion of 5-HT by the PCPA pre-treatment did not modify the effectiveness of MKC-242 ( Figure 2).…”

Section: Discussionsupporting

confidence: 43%

Effects of a benzodioxan derivative MKC-242 on the firing activity of the dorsal hippocampus CA1 pyramidal neurons in awake and urethane- anaesthetized rats: in vivo electrophysiological evidence for a 5-HT 1A agonistic property

Kasamo¹,

Suzuki²,

Tada³

et al. 2000

Int. J. Neuropsychopharm.

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“…Accordingly, the present data reaching a statistical significance seem more reliable than the previous ones. Several studies have demonstrated that such PCPA treatment depletes 5-HT in the hippocampus to less than 5% of the control level (Vanderwolf and Baker 1986;Kasamo et al 1994). Thus, it was feasible that the 5-HT depletion with PCPA increased the firing activity of the pyramidal neurons as indicated by the significantly higher values of the event rate and spike frequency of the PCPA group.…”

Section: Discussionmentioning

confidence: 99%

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

Kasamo

2001

Neuropsychopharmacology

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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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“…In a previous study , we used propranolol, an antagonist of ␤-adrenergic receptors, to test for the ␤-adrenergic dependence of emotional reinforcement. This drug also has a high affinity for serotonergic receptor subtypes (Kasamo et al, 1994;Hentall et al, 2000;Zhelyazkova-Savova and Zhelyazkov, 2003). To increase the specificity of ␤-adrenergic receptor blockade in the present study, we used timolol (Sigma, St. Louis, MO) as a reference antagonist.…”

Section: Methodsmentioning

confidence: 99%

Bidirectional Modulation of Hippocampal Long-Term Potentiation under Stress and No-Stress Conditions in Basolateral Amygdala-Lesioned and Intact Rats

Korz¹,

Frey²

2005

J. Neurosci.

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Hippocampal long-term potentiation (LTP) is widely considered as a cellular model for learning and memory formation. We have shown previously that protein synthesis-independent, early dentate gyrus (DG) LTP, lasting ϳ4 -5 h, can be transformed into a late-LTP with a duration of Ն24 h by a brief acute swim stress experience (high-stress condition). This reinforcement requires the activation of mineralocorticoid receptors and protein synthesis. The basolateral amygdala (BLA) is known to modulate glucocorticoid effects on the consolidation of spatial/contextual memory via a ␤-adrenergic mechanism. Interestingly, hippocampal DG-LTP can also be indirectly modulated by ␤-adrenergic and cholinergic/muscarinergic processes. Here, we show that the reinforcement of early-DG-LTP under high-stress conditions depends on the processing of novel spatial/contextual information. Furthermore, this reinforcement was blocked in BLA-lesioned animals compared with sham-operated and intact controls; however, it was not dependent on ␤-adrenergic or cholinergic/muscarinergic receptor activation. In contrast, under low-stress conditions, the induction of late-LTP in BLA-lesioned animals is facilitated, and this facilitation, again, was dependent on ␤-adrenergic activation. The data suggest that DG-LTP maintenance can be influenced by the BLA through different mechanisms: a short-lasting corticosterone-dependent and ␤-adrenergic-independent mechanism and a long-lasting mechanism that facilitated hippocampal ␤-adrenergic mechanisms.

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Effects of several 5-HT1A agonists on hippocampal rhythmical slow activity in unanesthetized rats

Cited by 6 publications

References 35 publications

Effects of a benzodioxan derivative MKC-242 on the firing activity of the dorsal hippocampus CA1 pyramidal neurons in awake and urethane- anaesthetized rats: in vivo electrophysiological evidence for a 5-HT 1A agonistic property

Effects of a benzodioxan derivative MKC-242 on the firing activity of the dorsal hippocampus CA1 pyramidal neurons in awake and urethane- anaesthetized rats: in vivo electrophysiological evidence for a 5-HT 1A agonistic property

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

Bidirectional Modulation of Hippocampal Long-Term Potentiation under Stress and No-Stress Conditions in Basolateral Amygdala-Lesioned and Intact Rats

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