Calcitonin receptor signaling in nucleus accumbens D1R- and D2R-expressing medium spiny neurons bidirectionally alters opioid taking in male rats

Zhang, Yafang; Nathan, Jennifer Ben; Moreno, Amanda; Merkel, Riley; Kahng, Michelle W; Hayes, Matthew R.; Reiner, Benjamin C.; Crist, Richard C.; Schmidt, Heath D.

doi:10.1038/s41386-023-01634-z

Cited by 4 publications

(2 citation statements)

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“…Of the differentially expressed genes in these categories, decreased expression of Igf1 (insulin‐like growth factor 1) is a standout, as recent work in the prefrontal cortex showed decreased IGF1 protein in mice that self‐administered oral fentanyl, and IGF1 replacement in the PFC attenuated fentanyl seeking behaviour 36 . Decreased expression of Calcr (calcitonin receptor) is another intriguing target, as Calcr expression has bidirectional effects on opioid self‐administration in nucleus accumbens neuron subtypes 37 . The top upregulated genes in dopamine neurons was the extracellular matrix protein Ecel1 , and the actin polymerization regulator Diaph3 , both of which are implicated in synaptic function and structural remodelling.…”

Section: Discussionmentioning

confidence: 99%

“… 36 Decreased expression of Calcr (calcitonin receptor) is another intriguing target, as Calcr expression has bidirectional effects on opioid self‐administration in nucleus accumbens neuron subtypes. 37 The top upregulated genes in dopamine neurons was the extracellular matrix protein Ecel1 , and the actin polymerization regulator Diaph3 , both of which are implicated in synaptic function and structural remodelling. These will be interesting gene targets to explore, as chronic morphine is known to induce structural plasticity of VTA dopamine neurons, 11 , 38 , 39 and extracellular matrix proteins are an area of interest in the opioid use disorder field.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional signatures of fentanyl use in the mouse ventral tegmental area

Fox,

Montemarano,

Ostman

et al. 2024

Addiction Biology

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Synthetic opioids such as fentanyl contribute to the vast majority of opioid‐related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse; however, it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes. Here, we performed single nuclei RNA sequencing to study transcriptional programs in fentanyl‐experienced mice. Male and female C57/BL6 mice self‐administered intravenous fentanyl (1.5 μg/kg/infusion) or saline for 10 days. After 24 h abstinence, VTA nuclei were isolated and prepared for sequencing on the 10× platform. We identified different patterns of gene expression across cell types. In dopamine neurons, we found enrichment of genes involved in growth hormone signalling. In dopamine‐glutamate‐GABA combinatorial neurons, and some GABA neurons, we found enrichment of genes involved in Pi3k‐Akt signalling. In glutamate neurons, we found enrichment of genes involved in cholinergic signalling. We identified transcriptional regulators for the differentially expressed genes in each neuron cluster, including downregulated transcriptional repressor Bcl6, and upregulated transcription factor Tcf4. We also compared the fentanyl‐induced gene expression changes identified in mouse VTA with a published rat dataset in bulk VTA, and found overlap in genes related to GABAergic signalling and extracellular matrix interaction. Together, we provide a comprehensive picture of how fentanyl self‐administration alters the transcriptional landscape of the mouse VTA that serves as the foundation for future mechanistic studies.

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Section: Discussionmentioning

confidence: 99%