PDE4 Inhibition Restores the Balance Between Excitation and Inhibition in VTA Dopamine Neurons Disrupted by Repeated In Vivo Cocaine Exposure

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Xiaojie LiuQing-song Liu

Abstract

Phosphodiesterase type 4 (PDE4) is a family of enzymes that selectively degrade intracellular cAMP. PDE4 inhibitors have been shown to regulate the rewarding and reinforcing effects of cocaine, but the underlying mechanisms remain poorly understood. Here we show that pretreatments with the PDE4 inhibitor rolipram attenuated cocaine-induced locomotor sensitization in mice. Repeated cocaine exposure in vivo caused a decrease in inhibitory postsynaptic currents (IPSCs) and an increase in the AMPAR/NMDAR ratio in ventral tegmental area (VTA) dopamine neurons in midbrain slices ex vivo. Cocaine exposure disrupted the balance between excitation and inhibition as shown by an increase in the excitation to inhibition (E/I) ratio. Rolipram pretreatments in vivo prevented cocaine-induced reductions in GABAergic inhibition but did not further increase cocaine-induced potentiation of excitation, leading to the restoration of a balance between excitation and inhibition and normalization of the E/I ratio. In support of this idea, we found that repeated cocaine exposure led to an increase in the single-unit action potential firing rate in vivo in VTA dopamine neurons, which was blocked by rolipram pretreatments. These results suggest that repe...Continue Reading

References

May 1, 1992·The Journal of Physiology·S W Johnson, R A North
May 30, 2001·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Q D WalkerC M Kuhn
Aug 8, 2001·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·W Schultz
Dec 21, 2002·The Journal of Biological Chemistry·Marco ContiCatherine Jin
Aug 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stephanie L BorglandAntonello Bonci
Nov 4, 2004·Journal of Receptor and Signal Transduction Research·Kim A NeveHeather Trantham-Davidson
Apr 7, 2006·Handbook of Experimental Pharmacology·A C Howlett
Aug 18, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zheng-Xiong XiEliot L Gardner
Nov 6, 2007·TheScientificWorldJournal·L L PeoplesK Guillem
Feb 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bin PanQing-song Liu
Sep 12, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Emanuela ArgilliAntonello Bonci
Mar 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Frédéric BrischouxMark A Ungless
Jul 7, 2009·Annual Review of Physiology·Boris D Heifets, Pablo E Castillo
May 28, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chiayu Q ChiuPablo E Castillo
Apr 22, 2011·Psychopharmacology·Wei HuHan-Ting Zhang
Apr 23, 2011·Neuropharmacology·Anne Marie WissmanCatherine S Woolley
Jun 21, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Peng ZhongQing-Song Liu
Sep 15, 2012·Psychopharmacology·Amanda E D Van SwearingenCynthia M Kuhn
Oct 9, 2012·Neuron·Nicolas X Tritsch, Bernardo L Sabatini
Jan 26, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Fei YuQing-Song Liu
Apr 19, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mami OtakaYan Dong
Apr 19, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Masago IshikawaYan Dong
Feb 6, 2014·Progress in Neuro-psychopharmacology & Biological Psychiatry·Huikun Wang, Carl R Lupica
May 17, 2014·The International Journal of Neuropsychopharmacology·Miaojun LaiWenhua Zhou
Jul 22, 2014·Nature·Mingshan XueMassimo Scanziani
Aug 28, 2014·Current Pharmaceutical Design·Rui-Ting WenHan-Ting Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Related Papers

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Peng ZhongQing-song Liu
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Bin PanQing-song Liu
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Peng ZhongQing-song Liu
© 2022 Meta ULC. All rights reserved