ArticleThe international journal of neuropsychopharmacology2023
IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice.
Article in The international journal of neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Insulin and IGF signaling in the brain: multilevel regulation of synaptic and network homeostasis.Frontiers in endocrinology · 2026Review
- Stra8 links neuronal activity to inhibitory circuit protection in the adult mouse brain.Cell reports · 2025Article
- The effect of intracerebroventricular injection of insulin-like growth factor-1 on morphine-induced conditioned place preference extinction and reinstatement; a behavioral and biochemical experimental study.Behavioral and brain functions : BBF · 2025Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Insulin-Like Growth Factor Binding Protein 2 Drives Neurodegeneration in Parkinson's Disease: Insights From In Vivo and In Vitro Studies.CNS neuroscience & therapeutics · 2024Article
- Transcriptional signatures of fentanyl use in the mouse ventral tegmental area.Addiction biology · 2024Article
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Authors and funding
5 authors at 1 institution in 2 countries.
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Abstract
backgroundOpioid use disorder (OUD) is a chronic relapsing psychiatric disorder with an enormous socioeconomic burden. Opioid overdose deaths have reached an epidemic level, especially for fentanyl. One of the biggest challenges to treat OUD is the relapse to drug seeking after prolonged abstinence. Abnormalities in insulin-like growth factor-1 (IGF-1) have been reported in various neurological and psychiatric disorders, including OUD. However, whether IGF-1 and its downstream signaling pathways are associated with relapse to fentanyl seeking remains unclear.
methodsMice were subjected to daily 2-hour fentanyl (10 μg/mL, 27 μL/infusion) oral self-administration training for 14 days, followed by 14-day fentanyl cessation. Expression levels of IGF-1/IGF-1 receptor and downstream signaling pathways in the dorsomedial prefrontal cortex (dmPFC) were detected. Then, IGF-1 was bilaterally microinjected into the dmPFC from fentanyl cessation day 9 to day 13. Fentanyl-seeking behavior and excitatory synaptic transmission of pyramidal neurons in PFC were evaluated.
resultsWe found that 14-day cessation from fentanyl oral self-administration caused significant downregulation of IGF-1 and IGF-1 receptor phosphorylation in the dmPFC. These changes were accompanied by inhibition of the downstream Akt and S6 signaling pathway. In addition, local administration of IGF-1 in the dmPFC attenuated context-induced fentanyl-seeking behavior. Furthermore, electrophysiology and immunohistochemistry analyses showed that IGF-1 blocked fentanyl-induced reduction of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors-mediated excitatory synaptic transmission as well as synaptic expression of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and N-methyl-D-aspartate receptor subunits.
conclusionsThese results suggest that IGF-1 in the PFC plays a pivotal role in regulating fentanyl seeking after prolonged cessation from fentanyl oral self-administration.
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