# Ventral pallidal circuitry in alcohol seeking and reinstatement by stress

> **NIH NIH R00** · UNIVERSITY OF MINNESOTA · 2020 · $249,000

## Abstract

Project Summary
 Acute or chronic stress contributes to both escalation of alcohol use and relapse to alcohol seeking after
abstinence. Stressors are hypothesized to contribute to relapse in part by promoting responses to cues in the
environment that have been previously associated with alcohol availability, yet the brain mechanisms of this
interaction between cues and stress are poorly understood. An area of the brain implicated in both stress- and
cue-induced reward seeking is the ventral pallidum (VP). I have previously found that VP neurons encode the
vigor of cue-elicited reward seeking, and my preliminary results suggest that VP neurons encode reinstatement
of reward seeking by the pharmacological stressor, yohimbine. In the current proposal, I aim to confirm and
expand my findings regarding VP encoding of reinstatement by stress, using a behavioral stressor, and to further
dissect the neural circuit mechanisms by which VP neurons contribute to alcohol seeking.
 Here, in the K99 phase, I will examine VP encoding of cued alcohol seeking and reinstatement induced
by stress in dependent versus non-dependent alcohol seeking rats. This aim will provide me with new training in
models of alcohol dependence and stress reinstatement. I will then examine encoding of alcohol seeking
behavior in inputs to VP from the prefrontal cortex (PFC) and basolateral amygdala (BLA), using a novel method
for projection specific measurement of activity. This method, fiber photometry, uses viral-based expression of a
fluorescent calcium indicator paired with optical measurement of fluorescence. Training in this skill will allow me
to measure projection-specific neural activity in the proposed aims and future projects. Further, this aim will
provide critical information regarding the timing of activity in BLA and PFC inputs during alcohol seeking, to be
tested in the R00 phase. I will also assess the collateralization of these neurons, comparing two methods:
traditional sectioning and immunolabeling-enabled three-dimensional imaging of solvent-cleared organs
(iDISCO). This method provides unprecedented access to the three-dimensional structure of immunolabeled
cells, and the opportunity to obtain both large-scale and high resolution information simultaneously, crucial for
planned experiments in my future laboratory.
 In the R00 phase I will test the functional role of temporally precise activity in BLA and PFC inputs to VP
during cued alcohol seeking and reinstatement of alcohol seeking, using optogenetics. I will also measure activity
in genetically-defined populations of neurons projecting from the nucleus accumbens (NAc), which include both
D1- and D2-dopamine receptor dominant neurons. Using transgenic rats I will selectively express calcium
indicators in either D1- or D2-dominant neurons projecting to VP. These experiments will provide novel data
regarding the differential activity of D1 and D2 neurons projecting to VP and will provide an important framework
for...

## Key facts

- **NIH application ID:** 9941012
- **Project number:** 5R00AA025384-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Jocelyn M Richard
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941012

## Citation

> US National Institutes of Health, RePORTER application 9941012, Ventral pallidal circuitry in alcohol seeking and reinstatement by stress (5R00AA025384-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9941012. Licensed CC0.

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