ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
PDE4 Inhibition Restores the Balance Between Excitation and Inhibition in VTA Dopamine Neurons Disrupted by Repeated In Vivo Cocaine Exposure.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Ibudilast, a neuroimmune modulator, reduces heavy drinking and alcohol cue-elicited neural activation: a randomized trial.Translational psychiatry · 2021Trial
- PDE4 inhibitor rolipram dynamically regulates the balance between D1-MSNs and D2-MSNs in the DMS to modulate abnormal "Go" behavior associated with alcohol addiction.Acta pharmacologica Sinica · 2026Article
- Pharmacological characterization and preclinical evaluation of 11h: a novel, brain-penetrant PDE4 inhibitor for neurological disorders.Frontiers in pharmacology · 2025Article
- Imaging neuroinflammation in individuals with substance use disorders.The Journal of clinical investigation · 2024Review
- cAMP-mediated upregulation of HCN channels in VTA dopamine neurons promotes cocaine reinforcement.Molecular psychiatry · 2023Article
- The Genetically Informed Neurobiology of Addiction (GINA) model.Nature reviews. Neuroscience · 2023Review
- Treadmill Exercise Reduces Neuroinflammation, Glial Cell Activation and Improves Synaptic Transmission in the Prefrontal Cortex in 3 × Tg-AD Mice.International journal of molecular sciences · 2022Article
- Article
- CB2 Agonist GW842166x Protected against 6-OHDA-Induced Anxiogenic- and Depressive-Related Behaviors in Mice.Biomedicines · 2022Article
- Ibudilast attenuates cocaine self-administration and prime- and cue-induced reinstatement of cocaine seeking in rats.Neuropharmacology · 2021Article
- Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine.Scientific reports · 2021Article
- KVA-D-88, a Novel Preferable Phosphodiesterase 4B Inhibitor, Decreases Cocaine-Mediated Reward PropertiesACS chemical neuroscience · 2020Article
- Synaptic and intrinsic plasticity in the ventral tegmental area after chronic cocaine.Current opinion in neurobiology · 2019Review
- Cyclic nucleotide phosphodiesterases: potential therapeutic targets for alcohol use disorder.Psychopharmacology · 2018Review
- Resveratrol modulates cocaine-induced inhibitory synaptic plasticity in VTA dopamine neurons by inhibiting phosphodiesterases (PDEs).Scientific reports · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
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 repeated cocaine exposure in vivo disrupts the balance between excitation and inhibition in VTA dopamine neurons, while PDE4 inhibition reestablishes the balance between excitation and inhibition through distinct mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.