# DBS Mechanisms of Morphine Extinction

> **NIH NIH SC2** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2020 · $150,000

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Barreto-Estrada JL
SUMMARY
DBS Mechanisms of Morphine Extinction
Deep brain stimulation (DBS) is a neurosurgical procedure that is used to treat neurologic and psychiatric
disorders. Recent research in both animals and humans has shown that DBS may be an effective procedure
for refractory addiction. We therefore propose to use DBS as treatment for drug-seeking behaviors in a rat
model. We previously found that high frequency DBS (HF-DBS) of the ventral striatum/nucleus accumbens
(VS/NAc) impaired extinction of morphine-induced conditioned place preference (CPP), whereas low frequency
DBS (LF-DBS) enhanced extinction memory (reducing drug seeking behavior). In other experiments (in the
absence of DBS), we demonstrated that animals showing good rate of morphine extinction exhibited an
increase in brain derived neurotrophic factor (BDNF) mRNA in the VS/NAc. In the present study, Aim 1 will
examine whether LF-DBS of the VS/NAc increases BDNF expression in key regions of the brain reward circuit
(i.e. PFC, amygdala, hippocampus and VS/NAc). In brief, rats expressing morphine-CPP will receive extinction
sessions, together with LF-DBS (20 Hz). After the extinction test day, rats will be sacrificed and brains will be
collected for Neu-N/BDNF immunohistochemistry. Aim 1.2 will test a cohort of animals to determine whether
LF-DBS is effective in female rats for morphine extinction. In Aim 2, the retrograde tracer cholera toxin subunit
B, conjugated to Alexa Fluor-555 (CTB) will be injected in the VS/NAc and tested in Morphine/fast-extinction
animals. This aim will be done in the absence of DBS (2.1-baseline) or in the presence of DBS (2.2-tracer
injected in IL) to determine the connectivity between brain regions associated with morphine extinction. In Aim
3.1 we will centrally infuse to IL, ANA-12, a BDNF receptor antagonist, while in Aim 3.2, systemic injections of
7,8DHF, a Trk B receptor agonist will be performed to behaviorally determine whether LF-DBS extinction
enhancement is mediated by BDNF signaling. Future interventions of treatment-resistant patients will benefit of
the characterization of the cellular and behavioral domains underlying morphine extinction after LF-DBS.
OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page

## Key facts

- **NIH application ID:** 9954057
- **Project number:** 5SC2DA047809-03
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** Jennifer Luz Barreto Estrada
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954057

## Citation

> US National Institutes of Health, RePORTER application 9954057, DBS Mechanisms of Morphine Extinction (5SC2DA047809-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954057. Licensed CC0.

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