# Chronic morphine: Regulation of ion conductances

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $346,500

## Abstract

PROJECT SUMMARY
Mu-opioid receptors are widely distributed in the central and peripheral nervous
system and upon activation have manifold actions including; depression of
respiration, activation of the reward pathway, disruption of normal
gastrointestinal motility and analgesia. Chronic administration of opioids results
in a decline in the response (tolerance) the degree of which differs depending on
the agonist and the measure under study. Analgesic tolerance to opioids limits
the therapeutic efficacy. The link between the initial activation of receptors and
the development of long-term tolerance is the subject of intense study and is
dependent on multiple mechanisms.
One repeatable and robust measure of opioid action measured on single cells is
acute desensitization. This is thought to be an initial adaptive step in the pathway
to cellular tolerance. Studies of desensitization have centered on (1) agonist
occupancy (2) receptor phosphorylation (3) arrestin binding and (4) receptor
internalization. By examining receptors where phosphorylation is blocked this
proposal will determine the link between desensitization and the development of
long-term tolerance. There are two possible outcomes. One is that the block of
desensitization disrupts the development of long-term tolerance measured at the
cellular level. The second is that the block of desensitization results in continued
signaling that augments homeostatic mechanisms at the cellular and synaptic
level that counter the continued activation of receptors.
The results from this study will address a long-standing question surrounding the
mechanisms that underlie a significant therapeutic problem with the use of
opioids as analgesics.

## Key facts

- **NIH application ID:** 10133559
- **Project number:** 5R01DA008163-29
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** John T Williams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,500
- **Award type:** 5
- **Project period:** 1993-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133559

## Citation

> US National Institutes of Health, RePORTER application 10133559, Chronic morphine: Regulation of ion conductances (5R01DA008163-29). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10133559. Licensed CC0.

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