Morphine-induced modulation of LTD at GABAergic synapses in the ventral tegmental area

Dacher, Matthieu; Nugent, Fereshteh S.

doi:10.1016/j.neuropharm.2010.11.012

Cited by 43 publications

(56 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). Previous studies have also shown that a single in vivo injection of morphine is able to trigger long-lasting changes in synaptic strength of GABAergic synapses (Dacher and Nugent 2011;Nugent et al 2007). Here we demonstrated (pA) saline (12) morphine (13) saline+CI-994 (5) morphine+CI-994(11) * * * * * * before after that morphine per se induced a reduction in GABAergic synaptic strength by suppressing GABA release and decreasing the number or function of postsynaptic GABA A Rs (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…Long-term potentiation (LTP) of glutamatergic synapses onto VTA DA neurons can be triggered 24 h after a single in vivo exposure to opioids and other drugs promoting DA cell excitability and behavioral sensitization (Brown et al 2010;Saal et al 2003;Ungless et al 2001). Moreover, a single exposure to a drug of abuse such as morphine has been shown to block LTP and may occlude long-term depression (LTD) at GABAergic synapses onto VTA DA neurons, further enhancing DA signaling from the VTA (Dacher and Nugent 2011;Nugent et al 2007).…”

Section: Learning Mechanisms In Brain Reward Pathways Are Hijacked Afmentioning

confidence: 99%

See 1 more Smart Citation

Morphine-induced synaptic plasticity in the VTA is reversed by HDAC inhibition

Authement

Langlois

Kassis

et al. 2016

Journal of Neurophysiology

Self Cite

View full text Add to dashboard Cite

Dopamine (DA) dysfunction originating from the ventral tegmental area (VTA) occurs as a result of synaptic abnormalities following consumption of drugs of abuse and underlies behavioral plasticity associated with drug abuse. Drugs of abuse can cause changes in gene expression through epigenetic mechanisms in the brain that underlie some of the lasting neuroplasticity and behavior associated with addiction. Here we investigated the function of histone acetylation and histone deacetylase (HDAC)2 in the VTA in recovery of morphine-induced synaptic modifications following a single in vivo exposure to morphine. Using a combination of immunohistochemistry, Western blot, and whole cell patch-clamp recording in rat midbrain slices, we show that morphine increased HDAC2 activity in VTA DA neurons and reduced histone H3 acetylation at lysine 9 (Ac-H3K9) in the VTA 24 h after the injection. Morphine-induced synaptic changes at glutamatergic synapses involved endocannabinoid signaling to reduce GABAergic synaptic strength onto VTA DA neurons. Both plasticities were recovered by in vitro incubation of midbrain slices with a class I-specific HDAC inhibitor (HDACi), CI-994, through an increase in acetylation of histone H3K9. Interestingly, HDACi incubation also increased levels of Ac-H3K9 and triggered GABAergic and glutamatergic plasticities in DA neurons of saline-treated rats. Our results suggest that acute morphine-induced changes in VTA DA activity and synaptic transmission engage HDAC2 activity locally in the VTA to maintain synaptic modifications through histone hypoacetylation. ventral tegmental area; synaptic plasticity; electrophysiology; synaptic transmission; histone deacetylase

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Learning Mechanisms In Brain Reward Pathways Are Hijacked Afmentioning

confidence: 99%

Morphine-induced synaptic plasticity in the VTA is reversed by HDAC inhibition

Authement

Langlois

Kassis

et al. 2016

Journal of Neurophysiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…This effect was also not dependent on endocannabinoid signaling, but was blocked by the dopamine D2 receptor (D2R) antagonist sulpiride. Interestingly, a single morphine injection was sufficient to prevent LFS-induced LTD GABA 24 hours after administration, suggesting that morphine can bidirectionally regulate GABA plasticity in VTA (Dacher and Nugent 2011a).…”

Section: Acute Opiate-induced Synaptic Plasticitymentioning

confidence: 98%

“…More recently, another form of VTA GABAergic plasticity has been described: longterm depression of GABAergic synapses onto DA neurons (LTD GABA ) (Dacher and Nugent 2011a). Using low-frequency stimulation (LFS), a stable LTD GABA in DA cells was induced that, in contrast to LTP GABA , was expressed postsynaptically and did not depend on NMDAR.…”

Section: Acute Opiate-induced Synaptic Plasticitymentioning

confidence: 99%

Opiate-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area and Locus Coeruleus Catecholamine Neurons

Mazei-Robison¹,

Nestler²

2012

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

The study of neuronal adaptations induced by opiate drugs is particularly relevant today given their widespread prescription and nonprescription use. Although much is known about the acute actions of such drugs on the nervous system, a great deal of work remains to fully understand their chronic effects. Here, we focus on longer-lasting adaptations that occur in two catecholaminergic brain regions that mediate distinct behavioral actions of opiates: ventral tegmental area (VTA) dopaminergic neurons, important for drug reward, and locus coeruleus (LC) noradrenergic neurons, important for physical dependence and withdrawal. We focus on changes in cellular, synaptic, and structural plasticity in these brain regions that contribute to opiate dependence and addiction. Understanding the molecular determinants of this opiate -induced plasticity will be critical for the development of better treatments for opiate addiction and perhaps safer opiate drugs for medicinal use.

show abstract

“…This D 2 R activation requires a neurochemical signaling via inhibitory G protein-PKA-inositol phosphate receptor IP 3 R-Ca 2+ -calcineurin-A-kinase anchoring protein 150 AKAP150 at GABAergic synapses (Dacher et al, 2013). Importantly, LTD GABA is abolished/occluded by a single dose of morphine 24 hours before the measurements (Dacher and Nugent, 2011a). Collectively, morphine-induced changes in LTP GABA and LTD GABA represent forms of inhibitory plasticity that together with changes in excitatory synapses provide a mechanism to enhance mesolimbic DA transmission and thereby increase the incentive properties of morphine (Dacher and Nugent, 2011b).…”

Section: G Opioid-induced Neural Adaptationsmentioning

confidence: 99%