ArticleProceedings of the National Academy of Sciences of the United States of America2011
Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- AlteredbioRxiv : the preprint server for biology · 2025Article
- Selectively counteracting cerebellar adaptations to chronic alcohol exposure reduces acute alcohol withdrawal severity in C57BL6/N mice.Neuropharmacology · 2025Article
- Control of action potential afterdepolarizations in the inferior olive by inactivating A-type currents through KThe Journal of physiology · 2025Article
- Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques.Neurobiology of stress · 2024Article
- Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques.bioRxiv : the preprint server for biology · 2024Article
- GDNF gene therapy for alcohol use disorder in male non-human primates.Nature medicine · 2023Article
- Synaptic effects of IL-1β and CRF in the central amygdala after protracted alcohol abstinence in male rhesus macaques.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Chronic Intermittent Ethanol Exposure Modulation of Glutamatergic Neurotransmission in Rat Lateral/Basolateral Amygdala is Duration-, Input-, and Sex-Dependent.Neuroscience · 2018Article
- On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome.Addiction biology · 2018Article
- The Cerebellar GABAHandbook of experimental pharmacology · 2018Article
- Transient Hypoxemia Chronically Disrupts Maturation of Preterm Fetal Ovine Subplate Neuron Arborization and Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2.Molecular psychiatry · 2017Article
- Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.Drug and alcohol dependence · 2017Article
- Studies using macaque monkeys to address excessive alcohol drinking and stress interactions.Neuropharmacology · 2017Review
- Recreational concentrations of alcohol enhance synaptic inhibition of cerebellar unipolar brush cells via pre- and postsynaptic mechanisms.Journal of neurophysiology · 2017Article
- Identifying Future Drinkers: Behavioral Analysis of Monkeys Initiating Drinking to Intoxication is Predictive of Future Drinking Classification.Alcoholism, clinical and experimental research · 2017Article
- Reprogramming of mPFC transcriptome and function in alcohol dependence.Genes, brain, and behavior · 2017Review
- Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Ethosuximide Reduces Mortality and Seizure Severity in Response to Pentylenetetrazole Treatment During Ethanol Withdrawal.Alcohol and alcoholism (Oxford, Oxfordshire) · 2015Article
- RNA interference of GluN1 inhibits neuronal rhythmogenesis in the adult inferior olive.Journal of molecular neuroscience : MN · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The brain adapts to chronic ethanol intoxication by altering synaptic and ion-channel function to increase excitability, a homeostatic counterbalance to inhibition by alcohol. Delirium tremens occurs when those adaptations are unmasked during withdrawal, but little is known about whether the primate brain returns to normal with repeated bouts of ethanol abuse and abstinence. Here, we show a form of bidirectional plasticity of pacemaking currents induced by chronic heavy drinking within the inferior olive of cynomolgus monkeys. Intracellular recordings of inferior olive neurons demonstrated that ethanol inhibited the tail current triggered by release from hyperpolarization (I(tail)). Both the slow deactivation of hyperpolarization-activated cyclic nucleotide-gated channels conducting the hyperpolarization-activated inward current and the activation of Ca(v)3.1 channels conducting the T-type calcium current (I(T)) contributed to I(tail), but ethanol inhibited only the I(T) component of I(tail). Recordings of inferior olive neurons obtained from chronically intoxicated monkeys revealed a significant up-regulation in I(tail) that was induced by 1 y of daily ethanol self-administration. The up-regulation was caused by a specific increase in I(T) which (i) greatly increased neurons' susceptibility for rebound excitation following hyperpolarization and (ii) may have accounted for intention tremors observed during ethanol withdrawal. In another set of monkeys, sustained abstinence produced the opposite effects: (i) a reduction in rebound excitability and (ii) a down-regulation of I(tail) caused by the down-regulation of both the hyperpolarization-activated inward current and I(T). Bidirectional plasticity of two hyperpolarization-sensitive currents following chronic ethanol abuse and abstinence may underlie persistent brain dysfunction in primates and be a target for therapy.
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