Faculty Collaboration Database

Resveratrol modulates cocaine-induced inhibitory synaptic plasticity in VTA dopamine neurons by inhibiting phosphodiesterases (PDEs). Sci Rep 2017 Nov 15;7(1):15657

Date

11/17/2017

Pubmed ID

29142291

Pubmed Central ID

PMC5688096

DOI

10.1038/s41598-017-16034-9

Scopus ID

2-s2.0-85034436814 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs). Resveratrol potentiated GABA_A and GABA_B-mediated inhibitory postsynaptic currents (IPSCs) in VTA dopamine neurons, and these effects were mediated by a protein kinase A (PKA)-dependent enhancement of presynaptic GABA release. In addition, we found that resveratrol blocked endocannabinoid-mediated long-term synaptic depression in VTA dopamine neurons. Resveratrol pretreatments attenuated cocaine-induced conditioned place preference and blocked the cocaine-induced reduction of GABAergic inhibition in VTA dopamine neurons. Together, these results provide evidence that resveratrol modulates basal inhibitory synaptic transmission, cocaine-induced synaptic plasticity, and drug-cue associative learning.

Author List

Li Y, Yu L, Zhao L, Zeng F, Liu QS

Author

Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aging
Animals
Cocaine
Cocaine-Related Disorders
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Dopaminergic Neurons
Endocannabinoids
GABAergic Neurons
Humans
Long-Term Synaptic Depression
Mice
Neuronal Plasticity
Neuroprotective Agents
Phosphodiesterase Inhibitors
Phosphoric Diester Hydrolases
Ventral Tegmental Area
gamma-Aminobutyric Acid