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Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin

The present study was aimed at characterizing the mechanisms by which neurotensin (NT) is acting within the ventral midbrain to induce a psychostimulant-like effect. In a first experiment, we determine which subtype(s) of NT receptors is/are involved in the reward-inducing effect of ventral midbrain...

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Autores principales: Rouibi, Khalil, Bose, Poulomee, Rompré, Pierre-Paul, Warren, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686738/
https://www.ncbi.nlm.nih.gov/pubmed/26733785
http://dx.doi.org/10.3389/fnins.2015.00470
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author Rouibi, Khalil
Bose, Poulomee
Rompré, Pierre-Paul
Warren, Richard A.
author_facet Rouibi, Khalil
Bose, Poulomee
Rompré, Pierre-Paul
Warren, Richard A.
author_sort Rouibi, Khalil
collection PubMed
description The present study was aimed at characterizing the mechanisms by which neurotensin (NT) is acting within the ventral midbrain to induce a psychostimulant-like effect. In a first experiment, we determine which subtype(s) of NT receptors is/are involved in the reward-inducing effect of ventral midbrain microinjection of NT using the conditioned place-preference (CPP) paradigm. In a second study, we used in vitro patch clamp recording technique to characterize the NT receptor subtype(s) involved in the modulation of glutamatergic neurotransmission (excitatory post-synaptic current, EPSC) in ventral tegmental neurons that expressed ([Formula: see text]), or do not express ([Formula: see text]), a hyperpolarization-activated cationic current. Behavioral studies were performed with adult male Long-Evans rats while electrophysiological recordings were obtained from brain slices of rat pups aged between 14 and 21 days. Results show that bilateral ventral midbrain microinjections of 1.5 and 3 nmol of D-Tyr[(11)]NT induced a CPP that was respectively attenuated or blocked by co-injection with 1.2 nmol of the NTS1/NTS2 antagonist, SR142948, and the preferred NTS1 antagonist, SR48692. In electrophysiological experiments, D-Tyr[(11)]NT (0.01-0.5 μM) attenuated glutamatergic EPSC in [Formula: see text] but enhanced it in [Formula: see text] neurons. The attenuation effect ([Formula: see text] neurons) was blocked by SR142948 (0.1 μM) while the enhancement effect ([Formula: see text] neurons) was blocked by both antagonists (0.1 μM). These findings suggest that (i) NT is acting on ventral midbrain NTS1 receptors to induce a rewarding effect and (ii) that this psychostimulant-like effect could be due to a direct action of NT on dopamine neurons and/or an enhancement of glutamatergic inputs to non-dopamine ([Formula: see text]) neurons.
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spelling pubmed-46867382016-01-05 Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin Rouibi, Khalil Bose, Poulomee Rompré, Pierre-Paul Warren, Richard A. Front Neurosci Pharmacology The present study was aimed at characterizing the mechanisms by which neurotensin (NT) is acting within the ventral midbrain to induce a psychostimulant-like effect. In a first experiment, we determine which subtype(s) of NT receptors is/are involved in the reward-inducing effect of ventral midbrain microinjection of NT using the conditioned place-preference (CPP) paradigm. In a second study, we used in vitro patch clamp recording technique to characterize the NT receptor subtype(s) involved in the modulation of glutamatergic neurotransmission (excitatory post-synaptic current, EPSC) in ventral tegmental neurons that expressed ([Formula: see text]), or do not express ([Formula: see text]), a hyperpolarization-activated cationic current. Behavioral studies were performed with adult male Long-Evans rats while electrophysiological recordings were obtained from brain slices of rat pups aged between 14 and 21 days. Results show that bilateral ventral midbrain microinjections of 1.5 and 3 nmol of D-Tyr[(11)]NT induced a CPP that was respectively attenuated or blocked by co-injection with 1.2 nmol of the NTS1/NTS2 antagonist, SR142948, and the preferred NTS1 antagonist, SR48692. In electrophysiological experiments, D-Tyr[(11)]NT (0.01-0.5 μM) attenuated glutamatergic EPSC in [Formula: see text] but enhanced it in [Formula: see text] neurons. The attenuation effect ([Formula: see text] neurons) was blocked by SR142948 (0.1 μM) while the enhancement effect ([Formula: see text] neurons) was blocked by both antagonists (0.1 μM). These findings suggest that (i) NT is acting on ventral midbrain NTS1 receptors to induce a rewarding effect and (ii) that this psychostimulant-like effect could be due to a direct action of NT on dopamine neurons and/or an enhancement of glutamatergic inputs to non-dopamine ([Formula: see text]) neurons. Frontiers Media S.A. 2015-12-22 /pmc/articles/PMC4686738/ /pubmed/26733785 http://dx.doi.org/10.3389/fnins.2015.00470 Text en Copyright © 2015 Rouibi, Bose, Rompré and Warren. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Rouibi, Khalil
Bose, Poulomee
Rompré, Pierre-Paul
Warren, Richard A.
Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin
title Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin
title_full Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin
title_fullStr Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin
title_full_unstemmed Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin
title_short Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin
title_sort ventral midbrain nts1 receptors mediate conditioned reward induced by the neurotensin analog, d-tyr[11]neurotensin
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686738/
https://www.ncbi.nlm.nih.gov/pubmed/26733785
http://dx.doi.org/10.3389/fnins.2015.00470
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