Cooperative CRF and α1 Adrenergic Signaling in the VTA Promotes NMDA Plasticity and Drives Social Stress Enhancement of Cocaine Conditioning

Jorge Tovar-Díaz, Matthew B. Pomrenze, Russell Kan, Bahram Pahlavan, Hitoshi Morikawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Stressful events rapidly trigger activity-dependent synaptic plasticity, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate appetitive learning, such as intake of addictive drugs. Using rats, we show that corticotropin-releasing factor (CRF) and α1 adrenergic receptor (α1AR) signaling enhance the plasticity of NMDA-receptor-mediated glutamatergic transmission in ventral tegmental area (VTA) dopamine (DA) neurons through distinct effects on inositol 1,4,5-triphosphate (IP 3 )-dependent Ca 2+ signaling. We find that CRF amplifies IP 3 -Ca 2+ signaling induced by stimulation of α1ARs, revealing a cooperative mechanism that promotes glutamatergic plasticity. In line with this, acute social defeat stress engages similar cooperative CRF and α1AR signaling in the VTA to enhance learning of cocaine-paired cues. These data provide evidence that CRF and α1ARs act in concert to regulate IP 3 -Ca 2+ signaling in the VTA and promote learning of drug-associated cues. Tovar-Díaz et al. demonstrate a cellular mechanism in which corticotropin-releasing factor (CRF) and α1 adrenergic receptors act in concert to regulate the induction of synaptic plasticity in VTA dopamine neurons and enhance cocaine place conditioning.

Original languageEnglish (US)
Pages (from-to)2756-2766
Number of pages11
JournalCell Reports
Volume22
Issue number10
DOIs
StatePublished - Mar 6 2018

Fingerprint

Ventral Tegmental Area
Corticotropin-Releasing Hormone
N-Methylaspartate
Cocaine
Adrenergic Agents
Plasticity
Adrenergic Receptors
Neuronal Plasticity
Dopaminergic Neurons
Learning
Neurons
Cues
Dopamine
Inositol 1,4,5-Trisphosphate
N-Methyl-D-Aspartate Receptors
Pharmaceutical Preparations
Rats
Conditioning (Psychology)
Drive
Data storage equipment

Keywords

  • CRF
  • Ca
  • IP
  • VTA
  • cocaine
  • dopamine neuron
  • reward learning
  • stress
  • α1AR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cooperative CRF and α1 Adrenergic Signaling in the VTA Promotes NMDA Plasticity and Drives Social Stress Enhancement of Cocaine Conditioning. / Tovar-Díaz, Jorge; Pomrenze, Matthew B.; Kan, Russell; Pahlavan, Bahram; Morikawa, Hitoshi.

In: Cell Reports, Vol. 22, No. 10, 06.03.2018, p. 2756-2766.

Research output: Contribution to journalArticle

Tovar-Díaz, Jorge ; Pomrenze, Matthew B. ; Kan, Russell ; Pahlavan, Bahram ; Morikawa, Hitoshi. / Cooperative CRF and α1 Adrenergic Signaling in the VTA Promotes NMDA Plasticity and Drives Social Stress Enhancement of Cocaine Conditioning. In: Cell Reports. 2018 ; Vol. 22, No. 10. pp. 2756-2766.
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