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

Frontiers in Behavioral Neuroscience

卷:8

Anne-Sophie eDelbes¹  Frederic eAmbroggi²  Sebastien eParnaudeau³  Francois eTronche⁴  Pier Vincenzo Piazza⁵  Serge H Luquet⁵  Celine eCansell⁵  Jacques eBARIK⁶  Marc eTuriault⁶  Marie-Louise eDongelmans⁶ 

[1] and the Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco;

[2] Center for Integrative Neuroscience;

[3] Columbia University;

[4] INSERM U862, NeuroCentre Magendie, Pathophysiology of Addiction.;

[5] Université Paris Diderot;

[6] Université Pierre et Marie Curie;

关键词: Glutamates;    Motivation;    Glucocorticoid receptor;    food reward;    stress response.;    dopamine pathway;   

DOI  :  10.3389/fnbeh.2014.00035

来源: DOAJ

【 摘 要 】

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 the 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 neurones 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.

【 授权许可】

Unknown