The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.

Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, the tachykinin NK3 receptor, one of the three tachykinin receptors in the brain, was s...

Full description

Bibliographic Details
Main Authors: De Souza Silva, MA, Mello, E, Müller, C, Jocham, G, Maior, R, Huston, J, Tomaz, C, Barros, M
Format: Journal article
Language:English
Published: 2006
_version_ 1797055405796360192
author De Souza Silva, MA
Mello, E
Müller, C
Jocham, G
Maior, R
Huston, J
Tomaz, C
Barros, M
author_facet De Souza Silva, MA
Mello, E
Müller, C
Jocham, G
Maior, R
Huston, J
Tomaz, C
Barros, M
author_sort De Souza Silva, MA
collection OXFORD
description Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, the tachykinin NK3 receptor, one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats. In order to test if these findings can be generalized to primates we investigated the role of the tachykinin NK3 receptor in the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with the tachykinin NK3 receptor antagonist, (R)-(N)-[1-[3-[1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4-yl]-N-methylacetamide (SR142801; 0, 0.02, 0.2, 2.0 mg/kg, i.p.), and received either a treatment with cocaine (10 mg/kg, i.p) or saline (i.p.). Cocaine increased locomotor activity and aerial glance behavior, but reduced exploratory and bodycare activities, scent marking and terrestrial scanning behavior. A sensitivity analysis revealed that two responder types can be differentiated in relation to the occurrence of a hyperlocomotor response to cocaine. SR142801 blocked the actions of cocaine on several behaviors dose-dependently for each responder type, respectively. There was no effect of SR142801 alone on any behavior measured. These data suggest that the tachykinin NK3 receptor contributes to the individual behavioral response to cocaine in marmoset monkeys. Having no behavioral effects on its own, but blocking the cocaine effects, might suggest the tachykinin NK3 receptor antagonist, SR142801, as a potential treatment of cocaine addiction in humans.
first_indexed 2024-03-06T19:10:15Z
format Journal article
id oxford-uuid:16894f76-5b88-40d3-844b-963c673ff268
institution University of Oxford
language English
last_indexed 2024-03-06T19:10:15Z
publishDate 2006
record_format dspace
spelling oxford-uuid:16894f76-5b88-40d3-844b-963c673ff2682022-03-26T10:31:51ZThe tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:16894f76-5b88-40d3-844b-963c673ff268EnglishSymplectic Elements at Oxford2006De Souza Silva, MAMello, EMüller, CJocham, GMaior, RHuston, JTomaz, CBarros, MBrain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, the tachykinin NK3 receptor, one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats. In order to test if these findings can be generalized to primates we investigated the role of the tachykinin NK3 receptor in the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with the tachykinin NK3 receptor antagonist, (R)-(N)-[1-[3-[1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4-yl]-N-methylacetamide (SR142801; 0, 0.02, 0.2, 2.0 mg/kg, i.p.), and received either a treatment with cocaine (10 mg/kg, i.p) or saline (i.p.). Cocaine increased locomotor activity and aerial glance behavior, but reduced exploratory and bodycare activities, scent marking and terrestrial scanning behavior. A sensitivity analysis revealed that two responder types can be differentiated in relation to the occurrence of a hyperlocomotor response to cocaine. SR142801 blocked the actions of cocaine on several behaviors dose-dependently for each responder type, respectively. There was no effect of SR142801 alone on any behavior measured. These data suggest that the tachykinin NK3 receptor contributes to the individual behavioral response to cocaine in marmoset monkeys. Having no behavioral effects on its own, but blocking the cocaine effects, might suggest the tachykinin NK3 receptor antagonist, SR142801, as a potential treatment of cocaine addiction in humans.
spellingShingle De Souza Silva, MA
Mello, E
Müller, C
Jocham, G
Maior, R
Huston, J
Tomaz, C
Barros, M
The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.
title The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.
title_full The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.
title_fullStr The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.
title_full_unstemmed The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.
title_short The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.
title_sort tachykinin nk3 receptor antagonist sr142801 blocks the behavioral effects of cocaine in marmoset monkeys
work_keys_str_mv AT desouzasilvama thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT melloe thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT mullerc thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT jochamg thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT maiorr thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT hustonj thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT tomazc thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT barrosm thetachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT desouzasilvama tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT melloe tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT mullerc tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT jochamg tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT maiorr tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT hustonj tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT tomazc tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys
AT barrosm tachykininnk3receptorantagonistsr142801blocksthebehavioraleffectsofcocaineinmarmosetmonkeys