Biomaterial Database

Effects of the 5-hydroxytryptamine receptor antagonist, BMY 7378, on 5-hydroxytryptamine neurotransmission: electrophysiological studies in the rat central nervous system. 1988

Y Chaput, and C de Montigny

Department of Psychiatry, McGill University, Montréal, Québec, Canada.

In the present electrophysiological studies, the effects of the putative 5-hydroxytryptamine (5-HT) receptor antagonist, BMY 7378, on the response of dorsal raphe nucleus 5-HT neurons and of CA3 dorsal hippocampus pyramidal neurons to 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were investigated in chloral hydrate-anesthetized rats. The effectiveness of microiontophoretically applied 5-HT and 8-OH-DPAT in suppressing the firing activity of both neuronal populations was assessed before and during the microiontophoretic application of BMY 7378. BMY 7378 reduced the effectiveness of 8-OH-DPAT, but not that of 5-HT, in depressing 5-HT neuron firing rate, whereas that of both agonists was reduced by concurrent application of BMY 7378 in the hippocampus. To assess whether endogenous 5-HT also could be antagonized, the response of pyramidal neurons to electrical activation of the 5-HT pathway was determined before and after i.v. BMY 7378. Low doses enhanced the efficacy of the stimulation, whereas higher doses decreased it. The latter finding suggests that BMY 7378 antagonizes the effect of endogenous 5-HT. Three procedures were used to investigate the enhancing effect of BMY 7378 on 5-HT synaptic transmission: 1) administration of BMY 7378 after terminal 5-HT autoreceptor blockade by methiothepin: methiothepin abolished the enhancing effect of BMY 7378; 2) blockade of the effect of RU 24969, a terminal 5-HT autoreceptor agonist: pretreatment with methiothepin, but not with BMY 7378, blocked the effect of RU 24969 on 5-HT synaptic transmission; and 3) administration of BMY 7378 during a reduced level of activation of terminal 5-HT autoreceptors, obtained by lowering the stimulation frequency from 1 to 0.5 Hz: the enhancing effect of BMY 7378 was reduced when the stimulation was delivered at 0.5 Hz. It is concluded that BMY 7378 is an effective antagonist of 5-HT1A receptors in vivo and that the mechanism of its enhancing effect on 5-HT transmission at low doses, although still undetermined, is not due to a competitive interaction at the terminal 5-HT autoreceptor.

UI	MeSH Term	Description	Entries
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297	Male		Males
D008719	Methiothepin	A serotonin receptor antagonist in the CENTRAL NERVOUS SYSTEM used as an antipsychotic.	Metitepine,Methiothepin Maleate,Methiothepine,Maleate, Methiothepin
D009435	Synaptic Transmission	The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.	Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
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.