Tags

Type your tag names separated by a space and hit enter

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.
Neuropharmacology. 1999 Jul; 38(7):1055-61.N

Abstract

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.

Authors+Show Affiliations

Cell Biology Division, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10428424

Citation

Scorza, C, et al. "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." Neuropharmacology, vol. 38, no. 7, 1999, pp. 1055-61.
Scorza C, Silveira R, Nichols DE, et al. 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. Neuropharmacology. 1999;38(7):1055-61.
Scorza, C., Silveira, R., Nichols, D. E., & Reyes-Parada, M. (1999). 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. Neuropharmacology, 38(7), 1055-61.
Scorza C, et al. 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. Neuropharmacology. 1999;38(7):1055-61. PubMed PMID: 10428424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Scorza,C, AU - Silveira,R, AU - Nichols,D E, AU - Reyes-Parada,M, PY - 1999/7/31/pubmed PY - 1999/7/31/medline PY - 1999/7/31/entrez SP - 1055 EP - 61 JF - Neuropharmacology JO - Neuropharmacology VL - 38 IS - 7 N2 - 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. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/10428424/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390899000234 DB - PRIME DP - Unbound Medicine ER -