Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

Sébastien Parnaudeau, Marie-Louise Dongelmans, Marc Turiault, Frédéric Ambroggi, Anne-Sophie Delbes, Céline Cansell, Serge Luquet, Pier-Vincenzo Piazza, François Tronche, Jacques Barik

Research output: Contribution to journalArticle

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Abstract

The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the glucocorticoid receptor (GR) a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While GR within dopamine-innervated areas drives cocaine's behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurons is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

Original languageEnglish
Article number35
JournalFrontiers in behavioral neuroscience
Volume8
DOIs
Publication statusPublished - 12 Feb 2014

Fingerprint

Glucocorticoid Receptors
Gene Silencing
Amphetamine
Dopamine
Dopaminergic Neurons
Reward
Glutamic Acid
Food
Limbic System
Nucleus Accumbens
Cocaine
Glucocorticoids
Substance-Related Disorders
Psychiatry
Transcription Factors
Hormones
Neurons
Injections
Pharmaceutical Preparations

Keywords

  • glucocorticoid receptor
  • dopamine pathway
  • glutamate
  • amphetamine
  • food reward
  • motivation

Cite this

Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine. / Parnaudeau, Sébastien; Dongelmans, Marie-Louise; Turiault, Marc; Ambroggi, Frédéric; Delbes, Anne-Sophie; Cansell, Céline; Luquet, Serge; Piazza, Pier-Vincenzo; Tronche, François; Barik, Jacques.

In: Frontiers in behavioral neuroscience, Vol. 8, 35, 12.02.2014.

Research output: Contribution to journalArticle

Parnaudeau, S, Dongelmans, M-L, Turiault, M, Ambroggi, F, Delbes, A-S, Cansell, C, Luquet, S, Piazza, P-V, Tronche, F & Barik, J 2014, 'Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine', Frontiers in behavioral neuroscience, vol. 8, 35. https://doi.org/10.3389/fnbeh.2014.00035
Parnaudeau, Sébastien ; Dongelmans, Marie-Louise ; Turiault, Marc ; Ambroggi, Frédéric ; Delbes, Anne-Sophie ; Cansell, Céline ; Luquet, Serge ; Piazza, Pier-Vincenzo ; Tronche, François ; Barik, Jacques. / Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine. In: Frontiers in behavioral neuroscience. 2014 ; Vol. 8.
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