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5-HT1A receptor-mediated inhibition of long-term potentiation in rat visual cortex

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Abstract

We investigated the effect of 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on the induction of long-term potentiation in rat visual cortex slices. Perfusion of 8-OH-DPAT (0.1–10 μM) did not affect layer II/III field potentials evoked by test stimulation of layer IV, but significantly reduced long-term potentiation induced by tetanic stimulation. The inhibitory effect of 8-OH-DPAT was blocked by the 5-HT1 receptor antagonist, pindolol (10 μM), but not by the 5-HT2,7 receptor antagonist, ritanserin (100 μM), nor by the 5-HT3,4 receptor antagonist, MDL72222 (100 μM). These results suggest that the rat visual cortex long-term potentiation is inhibited by 5-HT1A receptor stimulation.

Introduction

Serotonin (5-hydroxytryptamine, 5-HT) functions as a neurotransmitter or neuromodulator in the central nervous system. Serotonergic neurons are located mainly in the dorsal and medial raphe nuclei in the mesencephalon, and send neural projections to many brain regions, including the amygdala, hippocampus, septum, basal ganglia and cerebral cortex (Smith and Sweet, 1978). 5-HT contributes to many physiological functions in the central nervous system, including the control of blood pressure, body temperature, sleep, pain, anxiety and depression (Smith and Sweet, 1978; Iversen, 1984; Curzon, 1988). There is also evidence that 5-HT is involved in learning and memory (McEntee and Crook, 1991; Cassel and Jeltsch, 1995). 5-HT receptors are currently classified into seven families, with fourteen subtypes, based on their pharmacological properties and primary amino acid sequence (Humphrey et al., 1993; Hoyer and Martin, 1997). The 5-HT1A receptor is one of the best characterized 5-HT receptor subtypes.

Long-term potentiation of synaptic transmission is a form of activity-dependent synaptic plasticity that may underlie learning and memory (Bliss and Collingrige, 1993). The effect of 5-HT on long-term potentiation has been studied mainly in the hippocampus. 5-HT was first supposed to facilitate hippocampal long-term potentiation (Bliss et al., 1983; Klancnik and Phillips, 1991), but has recently been found to inhibit it (Corradetti et al., 1992; Villani and Johnston, 1993; Staubli and Otaky, 1994; Staubli and Xu, 1995). Furthermore, there is evidence that the 5-HT1A receptor mediates the inhibitory effect of 5-HT on hippocampal long-term potentiation (Sakai and Tanaka, 1993). However, it was unknown whether the 5-HT1A receptor contributes to the modulation of synaptic plasticity in other brain regions. In the present study, therefore, we investigated the role of 5-HT1A receptor in the induction of long-term potentiation in the rat primary visual cortex, a brain region that has been demonstrated to express 5-HT1A receptors (Wright et al., 1995).

Section snippets

Materials and methods

Whole brain was quickly isolated from male Wistar rats (3–5 weeks old; Nihon SLC, Shizuoka, Japan) and placed in ice-cold artificial cerebrospinal fluid consisting of (in mM): 124 NaCl, 5 KCl, 1.2 KH2PO4, 1.3 MgSO4, 2.4 CaCl2, 26 NaHCO3, 10 glucose, bubbled with 95% O2/5% CO2. The brain was trimmed to an occipital brain block containing the primary visual cortex, and then cut into slices of 400 μm thickness with a Vibratome (DTK-1500; Dosaka, Kyoto, Japan). The slices were allowed to recover

Results

As shown in Fig. 1B, layer II/III field potential evoked by test stimulation of layer IV often consisted of two negative-going waves, the fast component (N1) with about 2.0-ms peak latency and the late component (N2) with about 3.5-ms peak latency. When the perfusing medium was changed from normal artificial cerebrospinal fluid to Ca2+-free fluid, N2 disappeared completely and N1 remained unchanged, indicating that N1 and N2 represent non-synaptic and synaptic potentials, respectively. In

Discussion

We found that the 5-HT1A receptor agonist, 8-OH-DPAT, inhibited the induction of long-term potentiation in the rat visual cortex in vitro. Since long-term potentiation was normally induced after washout of 8-OH-DPAT, the inhibitory effect of 8-OH-DPAT is not caused by irreversible tissue damage. The inhibitory effect of 8-OH-DPAT was blocked by the presence of the 5-HT1 receptor antagonist, pindolol, supporting the assumption that the effect of 8-OH-DPAT results from 5-HT1A receptor

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