# Thalamic Circuits Underlying Opioid Seeking

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $449,618

## Abstract

Prescription opioid abuse is the fastest growing drug problem in the United States. Now, deaths from overdose 
of  opioid  pain  relievers  exceed  those  from  all  illegal  drugs.  Chronic  opioid  use  induces  opioid  dependence, 
which  is  characterized  by  extremely  unpleasant  physiological  and  psychological  symptoms  after  drug  use  is 
terminated.  Opioid users learn to associate opioid intake with relief from negative physical and affective states.  
This  maladaptive  association  might  last  long  after  withdrawal  has  terminated  and  underlie  the  drug  cravings 
experience  by  many  users  after  exposure  to  drug-­associated  cues  or  stressful  life  events.  We  have  recently 
identified  that  the  paraventricular  nucleus  of  the  thalamus  (PVT)  is  a  prominent  neuronal  substrate  mediating 
the  physical  signs  and  negative  emotion  accompanied  with  opioid  withdrawal,  which  provide  a  unique 
opportunity  to  directly  examine  the  contribution  of  withdrawal  states  to  opioid-­associated  memories.    In  this 
application,  we  propose  to  use  pathway  specific  optogenetic  and  pharmacogenetic  manipulation  (1)  to 
determining  roles  of  the  PVT  output  pathways  in  the  formation  and  maintenance  of  opioid-­associated 
memories;;  (2)  to  study  morphine  induced  plasticity  in  each  PVT  pathway  and  impact  of  pathway  silencing  on 
this  plasticity;;  (3)  we  will  combine  pathway  specific  manipulation  in  the  PVT,  c-­Fos  iDISCO+,  and  light  sheet 
fluorescent  microscopy  to  mapping  brain-­wide  network  activities  underlying  opioid-­associated  memories.  Our 
work will inspire the development of novel strategy to treat opioid abuse.

## Key facts

- **NIH application ID:** 10200726
- **Project number:** 5R01DA045664-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Xiaoke Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $449,618
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200726

## Citation

> US National Institutes of Health, RePORTER application 10200726, Thalamic Circuits Underlying Opioid Seeking (5R01DA045664-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200726. Licensed CC0.

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