ArticleThe Journal of comparative neurology2008
Increased AMPA receptor GluR1 subunit incorporation in rat hippocampal CA1 synapses during benzodiazepine withdrawal.
Article in The Journal of comparative neurology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Synaptic Adaptations in the Amygdala During Alprazolam Withdrawal: Insights from a Female Rat Model of Benzodiazepine Withdrawal.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Benzodiazepine Dependence: Clinical and Molecular Aspects, Preventive Strategies and Therapeutic Approaches.International journal of molecular sciences · 2026Review
- Early life exposure to clonazepam has both short- and long-term effects on seizures induced with pentylenetetrazol (PTZ).Frontiers in pharmacology · 2025Article
- GABAFrontiers in psychiatry · 2022Review
- Neonatal Clonazepam Administration Induces Long-Lasting Changes in Glutamate Receptors.Frontiers in molecular neuroscience · 2018Article
- BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Drug-evoked synaptic plasticity causing addictive behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Review
- Effects of nitric oxide synthase inhibition in the dorsolateral periaqueductal gray matter on ethanol withdrawal-induced anxiety-like behavior in rats.Psychopharmacology · 2013Article
- Distinct regional and subcellular localization of the actin-binding protein filamin A in the mature rat brain.The Journal of comparative neurology · 2012Article
- Regulation of Ca²⁺/calmodulin-dependent protein kinase II signaling within hippocampal glutamatergic postsynapses during flurazepam withdrawal.Neural plasticity · 2012Article
- Hippocampal GluR1 associates with behavior in the elevated plus maze and shows sex differences.Behavioural brain research · 2011Article
- Unraveling glutamate-opioid receptor interactions using high-resolution electron microscopy: implications for addiction-related processes.Experimental neurology · 2011Article
- Hooked on benzodiazepines: GABAA receptor subtypes and addiction.Trends in neurosciences · 2011Review
- Expression of the AMPA Receptor Subunits GluR1 and GluR2 is Associated with Granule Cell Maturation in the Dentate Gyrus.Frontiers in neuroscience · 2011Article
- Down-regulation of synaptic GluN2B subunit-containing N-methyl-D-aspartate receptors: a physiological brake on CA1 neuron α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hyperexcitability during benzodiazepine withdrawal.The Journal of pharmacology and experimental therapeutics · 2011Article
- Immunogold electron microscopic evidence of differential regulation of GluN1, GluN2A, and GluN2B, NMDA-type glutamate receptor subunits in rat hippocampal CA1 synapses during benzodiazepine withdrawal.The Journal of comparative neurology · 2010Article
- Calcium/calmodulin-dependent protein kinase II mediates hippocampal glutamatergic plasticity during benzodiazepine withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Article
- Glutamate plasticity in the drunken amygdala: the making of an anxious synapse.International review of neurobiology · 2010Review
- Chronic benzodiazepine-induced reduction in GABA(A) receptor-mediated synaptic currents in hippocampal CA1 pyramidal neurons prevented by prior nimodipine injection.Neuroscience · 2008Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Prolonged benzodiazepine treatment leads to tolerance and increases the risk of dependence. Flurazepam (FZP) withdrawal is associated with increased anxiety correlated with increased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPAR)-mediated synaptic function and AMPAR binding in CA1 pyramidal neurons. Enhanced AMPAR synaptic strength is also associated with a shift toward inward rectification of synaptic currents and increased expression of GluR1, but not GluR2, subunits, suggesting augmented membrane incorporation of GluR1-containing, GluR2-lacking AMPARs. To test this hypothesis, the postsynaptic incorporation of GluR1 and GluR2 subunits in CA1 neurons after FZP withdrawal was examined by postembedding immunogold quantitative electron microscopy. The percentage of GluR1 positively labeled stratum radiatum (SR) synapses was significantly increased in FZP-withdrawn rats (88.2% +/- 2.2%) compared with controls (74.4% +/- 1.9%). In addition, GluR1 immunogold density was significantly increased by 30% in SR synapses in CA1 neurons from FZP-withdrawn rats compared with control rats (FZP: 14.1 +/- 0.3 gold particles/mum; CON: 10.8 +/- 0.4 gold particles/mum). In contrast, GluR2 immunogold density was not significantly different between groups. Taken together with recent functional data from our laboratory, the current study suggests that the enhanced glutamatergic strength at CA1 neuron synapses during benzodiazepine withdrawal is mediated by increased incorporation of GluR1-containing AMPARs. Mechanisms underlying synaptic plasticity in this model of drug dependence are therefore fundamentally similar to those that operate during activity-dependent plasticity.
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Registered trials
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