# The role of ventral pallidal cannabinoid and opioid signaling in cross-sensitization between THC and cue-induced heroin seeking

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $224,250

## Abstract

Abstract
Cannabis could serve as a therapeutic alternative to opioids, however, preclinical studies using non-contingent
THC pre-exposure and a recent epidemiological study indicate that cannabis use can increase the risk for
future opioid abuse. Repeated drug exposure can lead to persistent hyper-reactivity to drugs and drug-
associated stimuli. The underlying neuroadaptations of this sensitization are thought to be involved in
increased drug seeking after chronic drug exposure. Cross-sensitization between drugs of abuse also occurs
and some drugs cross-sensitize better than others, indicating distinct neuroadaptations depending on drug-
class. However the neurobiological underpinnings of the enhanced responsiveness to heroin after THC pre-
exposure are unknown. It has been shown that sensitization to morphine depends on MOR signaling in the
Ventral pallidum (VP), however the lack of a preclinical model of chronic dual THC and heroin self-
administration (SA) impedes a detailed investigation of THC-induced neuroadaptations within the reward
pathway that could lead to cross-sensitization with opioids. I will employ a newly developed rat model of dual
THC and heroin SA to study whether THC intake augments future heroin self-administration and cue-induced
heroin seeking. I will investigate neuroadaptations in CB1R and MOR signaling in the VP after withdrawal from
chronic THC and heroin exposure and will compare to adaptations induced by either chronic THC or heroin
alone. I hypothesize that that THC and heroin exposure induce pathway specific adaptations in CB1 and MOR
signaling which potentiate D1 afferents and inhibit D2 afferents in the VP and that these cross-adaptations
contribute to facilitated cue-induced heroin seeking after THC pre-exposure.

## Key facts

- **NIH application ID:** 9978334
- **Project number:** 1R21DA048337-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Daniela Neuhofer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $224,250
- **Award type:** 1
- **Project period:** 2020-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978334

## Citation

> US National Institutes of Health, RePORTER application 9978334, The role of ventral pallidal cannabinoid and opioid signaling in cross-sensitization between THC and cue-induced heroin seeking (1R21DA048337-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978334. Licensed CC0.

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