Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action

The effects of two selective 5-HT-releasing agents, 4-methylthioamphetamine (MTA) and 5-methoxy-6-methyl-2-aminoindan (MMAI), on the extracellular 5-HT concentration in the dorsal hippocampus was determined by microdialysis in anesthetized rats. After i.p. administration of 1 or 5 mg/kg of either co...

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Bibliographic Details
Published in:Neuropharmacology 1999-07, Vol.38 (7), p.1055-1061
Main Authors: Scorza, Cecilia, Silveira, Rodolfo, Nichols, DavidE, Reyes-Parada, Miguel
Format: Article
Language:English
Subjects:
4-Methylthioamphetamine
5-HT Releasers
5-Methoxy-6-methyl-2-aminoindan
Amphetamines - pharmacology
Animals
Antidepressants
Antidepressive Agents - pharmacology
Biological and medical sciences
Hippocampus - drug effects
Hippocampus - metabolism
Indans - pharmacology
Male
Medical sciences
Microdialysis
Monoamine Oxidase - metabolism
Monoamino oxidase
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Rats, Sprague-Dawley
Serotonin
Serotonin - metabolism
Serotonin Antagonists - pharmacology
Serotonin Uptake Inhibitors - pharmacology
Serotoninergic system
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Summary:The effects of two selective 5-HT-releasing agents, 4-methylthioamphetamine (MTA) and 5-methoxy-6-methyl-2-aminoindan (MMAI), on the extracellular 5-HT concentration in the dorsal hippocampus was determined by microdialysis in anesthetized rats. After i.p. administration of 1 or 5 mg/kg of either compound, a rapid and significant increase of 5-HT basal release was observed. MTA (5 mg/kg) induced a maximal increase of about 2000% over the basal value 40 min after injection, which declined slowly, whereas MMAI (5 mg/kg) induced a maximal response of about 1350% which showed a rapid decline. Monoamine oxidase-A inhibitory properties of MTA, and MMAI’s lack of similar properties might account for the difference between the two compounds. In agreement with previous information, a much lower increase in hippocampal 5-HT was observed in response to systemic fluoxetine. This difference in the magnitude of the response after MTA or MMAI and fluoxetine indicates that different mechanisms of action are operating. Based on evidence showing that an acute enhancement of 5-HT neurotransmission might result in the rapid appearance of therapeutic effects of serotonergic antidepressants, we suggest that MTA and MMAI might serve as leads for a novel family of compounds with a short onset of action useful for treating depression.
ISSN:0028-3908
1873-7064
DOI:10.1016/S0028-3908(99)00023-4