ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Rescue of dopamine transporter function in hypoinsulinemic rats by a D2 receptor-ERK-dependent mechanism.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Behavioral manifestations and underlying mechanisms of amphetamine in constructing animal models of mania: a comprehensive review.Frontiers in neuroscience · 2025Review
- Trace Amine-Associated Receptors and Monoamine-Mediated Regulation of Insulin Secretion in Pancreatic Islets.Biomolecules · 2023Review
- Behaviorally penetrant, anomalous dopamine efflux exposes sex and circuit dependent regulation of dopamine transporters.Molecular psychiatry · 2022Article
- Striatal DAT availability does not change after supraphysiological glucose loading dose in humans.Endocrine connections · 2021Article
- In Situ Regulated Dopamine Transporter Trafficking: There's No Place Like Home.Neurochemical research · 2020Review
- Article
- Elucidating the Relationship Between Diabetes Mellitus and Parkinson's Disease UsingFrontiers in neuroscience · 2020Review
- Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress.The European journal of neuroscience · 2018Article
- Bile diversion, a bariatric surgery, and bile acid signaling reduce central cocaine reward.PLoS biology · 2018Article
- Region-Specific Regulation of Presynaptic Dopamine Homeostasis by DThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Amphetamine Reverses Escalated Cocaine Intake via Restoration of Dopamine Transporter Conformation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Article
- To Do or Not to Do: Dopamine, Affordability and the Economics of Opportunity.Frontiers in integrative neuroscience · 2018Article
- The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission.Nature communications · 2017Article
- Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain.Journal of neurochemistry · 2017Article
- High-Fat-Diet-Induced Deficits in Dopamine Terminal Function Are Reversed by Restoring Insulin Signaling.ACS chemical neuroscience · 2017Article
- An insulin resistance associated neural correlate of impulsivity in type 2 diabetes mellitus.PloS one · 2017Article
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
- High fat diet augments amphetamine sensitization in mice: Role of feeding pattern, obesity, and dopamine terminal changes.Neuropharmacology · 2016Article
- Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats.Drug and alcohol dependence · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
The dopamine (DA) transporter (DAT) is a major target for abused drugs and a key regulator of extracellular DA. A rapidly growing literature implicates insulin as an important regulator of DAT function. We showed previously that amphetamine (AMPH)-evoked DA release is markedly impaired in rats depleted of insulin with the diabetogenic agent streptozotocin (STZ). Similarly, functional magnetic resonance imaging experiments revealed that the blood oxygenation level-dependent signal following acute AMPH administration in STZ-treated rats is reduced. Here, we report that these deficits are restored by repeated, systemic administration of AMPH (1.78 mg/kg, every other day for 8 d). AMPH stimulates DA D(2) receptors indirectly by increasing extracellular DA. Supporting a role for D(2) receptors in mediating this "rescue," the effect was completely blocked by pre-treatment of STZ-treated rats with the D(2) receptor antagonist raclopride before systemic AMPH. D(2) receptors regulate DAT cell surface expression through ERK1/2 signaling. In ex vivo striatal preparations, repeated AMPH injections increased immunoreactivity of phosphorylated ERK1/2 (p-ERK1/2) in STZ-treated but not control rats. These data suggest that repeated exposure to AMPH can rescue, by activating D(2) receptors and p-ERK signaling, deficits in DAT function that result from hypoinsulinemia. Our data confirm the idea that disorders influencing insulin levels and/or signaling, such as diabetes and anorexia, can degrade DAT function and that insulin-independent pathways are present that may be exploited as potential therapeutic targets to restore normal DAT function.
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Registered trials
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.