Pre- and post-synaptic effects of the 5-HT3 agonist 2-methyl-5-HT on the 5-HT system in the rat brain. 1995

N Haddjeri, and P Blier
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Microiontophoretic applications of 5-HT and of the 5-HT3 agonist 2-methyl-5-HT produced a current-dependent suppression of firing activity of both hippocampal (CA1 and CA3) and cortical neurons in anesthetized rats. Concomitant microiontophoretic applications of the 5-HT3 antagonists BRL 46470A and S-zacopride, as well as their intravenous injection, did not antagonize the inhibitory effect of 5-HT and 2-methyl-5-HT. In contrast, the 5-HT1A antagonist BMY 7378, applied by microiontophoresis or administered intravenously, significantly reduced the inhibitory action of 5-HT and 2-methyl-5-HT. The firing activity of dorsal raphe 5-HT neurons was also reduced by 5-HT, 2-methyl-5-HT and the 5-HT1A agonist 8-OH-DPAT applied by microiontophoresis. While BRL 46470A (0.1 and 1 mg/kg, i.v.) did not antagonize the inhibitory effect of the three 5-HT agonists on 5-HT neuronal firing activity, only that of 8-OH-DPAT was attenuated by the 5-HT1A antagonist (+) WAY 100135. R-zacopride significantly reduced the duration of suppression of firing activity of CA3 pyramidal neurons induced by the electrical stimulation of the ascending 5-HT pathway, and this reducing effect was prevented by the three 5-HT3/5-HT4 antagonists renzapride, S-zacopride and tropisetron, but not by BRL 46470A. Finally, in in vitro superfusion experiments, both BRL 46470A and S-zacopride antagonized the enhancing action of 2-methyl-5-HT on the electrically-evoked release of [3H]-5-HT in both rat frontal cortex and hippocampus slices. These findings suggest that, in vivo, the suppressant effect of 2-methyl-5-HT on the firing activity of dorsal hippocampus pyramidal, somatosensory cortical, and dorsal raphe 5-HT neurons is not mediated by 5-HT3 receptors, but rather by 5-HT1A receptors. The attenuating effect of R-zacopride on the effectiveness of the stimulation of the ascending 5-HT pathway is not mediated by 5-HT3 receptors. In contrast, in vitro, the enhancing action of 2-methyl-5-HT on the electrically-evoked release of [3H]5-HT in both frontal cortex and hippocampus slices is mediated by 5-HT3 receptors.

UI MeSH Term Description Entries
D008297 Male Males
D009412 Nerve Fibers Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM. Cerebellar Mossy Fibers,Mossy Fibers, Cerebellar,Cerebellar Mossy Fiber,Mossy Fiber, Cerebellar,Nerve Fiber
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011903 Raphe Nuclei Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA. Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D013003 Somatosensory Cortex Area of the parietal lobe concerned with receiving sensations such as movement, pain, pressure, position, temperature, touch, and vibration. It lies posterior to the central sulcus. Brodmann Area 1,Brodmann Area 2,Brodmann Area 3,Brodmann Areas 1, 2, 3,Brodmann Areas 1, 2, and 3,Brodmann Areas 3, 1, 2,Brodmann Areas 3, 1, and 2,Brodmann's Area 1,Brodmann's Area 2,Brodmann's Area 3,Brodmann's Areas 1, 2, and 3,Brodmann's Areas 3, 1, and 2,Parietal-Opercular Cortex,Primary Somesthetic Area,S1 Cortex,S2 Cortex,SII Cortex,Anterior Parietal Cortex,Gyrus Postcentralis,Post Central Gyrus,Postcentral Gyrus,Primary Somatic Sensory Area,Primary Somatosensory Area,Primary Somatosensory Areas,Primary Somatosensory Cortex,SI Cortex,Second Somatic Sensory Area,Secondary Sensory Cortex,Secondary Somatosensory Area,Secondary Somatosensory Cortex,Area 1, Brodmann,Area 1, Brodmann's,Area 2, Brodmann,Area 2, Brodmann's,Area 3, Brodmann,Area 3, Brodmann's,Area, Primary Somatosensory,Area, Primary Somesthetic,Area, Secondary Somatosensory,Areas, Primary Somatosensory,Brodmanns Area 1,Brodmanns Area 2,Brodmanns Area 3,Cortex, Anterior Parietal,Cortex, Parietal-Opercular,Cortex, Primary Somatosensory,Cortex, S1,Cortex, S2,Cortex, SI,Cortex, SII,Cortex, Secondary Sensory,Cortex, Secondary Somatosensory,Cortex, Somatosensory,Gyrus, Post Central,Gyrus, Postcentral,Parietal Cortex, Anterior,Parietal Opercular Cortex,Parietal-Opercular Cortices,Primary Somatosensory Cortices,Primary Somesthetic Areas,S1 Cortices,S2 Cortices,SII Cortices,Secondary Somatosensory Areas,Sensory Cortex, Secondary,Somatosensory Area, Primary,Somatosensory Area, Secondary,Somatosensory Areas, Primary,Somatosensory Cortex, Primary,Somatosensory Cortex, Secondary,Somesthetic Area, Primary,Somesthetic Areas, Primary

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