ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Chronic morphine treatment impaired hippocampal long-term potentiation and spatial memory via accumulation of extracellular adenosine acting on adenosine A1 receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 93 citations in OpenAlex.
- Persistent effects of repeated adolescent and adult heroin vapor inhalation in female Wistar rats.Psychopharmacology · 2026Article
- High Morphine Use Disorder Susceptibility Is Predicted by Impaired Learning Ability in Mice.Brain sciences · 2022Article
- Chronic D-ribose and D-mannose overload induce depressive/anxiety-like behavior and spatial memory impairment in mice.Translational psychiatry · 2021Article
- The IntelliCage System: A Review of Its Utility as a Novel Behavioral Platform for a Rodent Model of Substance Use Disorder.Frontiers in behavioral neuroscience · 2021Review
- Mitragynine (Kratom)-Induced Cognitive Impairments in Mice Resemble Δ9-THC and Morphine Effects: Reversal by Cannabinoid CBFrontiers in pharmacology · 2021Article
- Indices of dentate gyrus neurogenesis are unaffected immediately after or following withdrawal from morphine self-administration compared to saline self-administering control male rats.Behavioural brain research · 2020Article
- Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats.Metabolic brain disease · 2020Article
- Effect of oleuropein on morphine-induced hippocampus neurotoxicity and memory impairments in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Behavioral and electrophysiological aspects of cognition in neonate rats lactated by morphine addicted mothers.Iranian journal of basic medical sciences · 2019Article
- Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease.Neurochemical research · 2019Review
- Adenosine A1 Receptors Play an Important Protective Role Against Cognitive Impairment and Long-Term Potentiation Inhibition in a Pentylenetetrazol Mouse Model of Epilepsy.Molecular neurobiology · 2018Article
- Pharmacological Blockade of Adenosine AFrontiers in pharmacology · 2018Article
- Activating Autophagy in Hippocampal Cells Alleviates the Morphine-Induced Memory Impairment.Molecular neurobiology · 2017Article
- Brain Reward Circuits in Morphine Addiction.Molecules and cells · 2016Review
- Adenosine A1 Receptor-Mediated Endocytosis of AMPA Receptors Contributes to Impairments in Long-Term Potentiation (LTP) in the Middle-Aged Rat Hippocampus.Neurochemical research · 2016Article
- Impact of chronic morphine on delta opioid receptor-expressing neurons in the mouse hippocampus.Neuroscience · 2016Article
- Cell type-specific effects of adenosine on cortical neurons.Cerebral cortex (New York, N.Y. : 1991) · 2015Article
- The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients.Scientific reports · 2015Article
- Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine.Journal of experimental neuroscience · 2015Article
- The combined inhibitory effect of the adenosine A1 and cannabinoid CB1 receptors on cAMP accumulation in the hippocampus is additive and independent of A1 receptor desensitization.BioMed research international · 2015Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic exposure to opiates impairs hippocampal long-term potentiation (LTP) and spatial memory, but the underlying mechanisms remain to be elucidated. Given the well known effects of adenosine, an important neuromodulator, on hippocampal neuronal excitability and synaptic plasticity, we investigated the potential effect of changes in adenosine concentrations on chronic morphine treatment-induced impairment of hippocampal CA1 LTP and spatial memory. We found that chronic treatment in mice with either increasing doses (20-100 mg/kg) of morphine for 7 d or equal daily dose (20 mg/kg) of morphine for 12 d led to a significant increase of hippocampal extracellular adenosine concentrations. Importantly, we found that accumulated adenosine contributed to the inhibition of the hippocampal CA1 LTP and impairment of spatial memory retrieval measured in the Morris water maze. Adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine significantly reversed chronic morphine-induced impairment of hippocampal CA1 LTP and spatial memory. Likewise, adenosine deaminase, which converts adenosine into the inactive metabolite inosine, restored impaired hippocampal CA1 LTP. We further found that adenosine accumulation was attributable to the alteration of adenosine uptake but not adenosine metabolisms. Bidirectional nucleoside transporters (ENT2) appeared to play a key role in the reduction of adenosine uptake. Changes in PKC-alpha/beta activity were correlated with the attenuation of the ENT2 function in the short-term (2 h) but not in the long-term (7 d) period after the termination of morphine treatment. This study reveals a potential mechanism by which chronic exposure to morphine leads to impairment of both hippocampal LTP and spatial memory.
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