How the brain enzyme PDE4 affects GABA receptors and drinking
PDE4 regulation of GABA-A receptors in alcohol tolerance and consumption
['FUNDING_R01'] · UNIVERSITY OF TEXAS AT AUSTIN · NIH-11121945
Looks at whether blocking the brain enzyme PDE4 can change GABA receptor activity to reduce alcohol tolerance and drinking in people with alcohol use disorder.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF TEXAS AT AUSTIN (nih funded) |
| Locations | 1 site (AUSTIN, UNITED STATES) |
| Trial ID | NIH-11121945 on ClinicalTrials.gov |
What this research studies
Researchers are using drugs that block PDE4 (for example, apremilast) to see how those drugs change GABAA receptor activity that helps determine how alcohol feels. They study how blocking PDE4 raises cAMP and activates PKA, which can add phosphate groups to GABAA β3 (and β1) subunits and alter receptor function. Most experiments use rodent models to measure acute alcohol tolerance and voluntary drinking and include laboratory tests of receptor phosphorylation and signaling. The team aims to connect these molecular changes to drinking behavior so the findings could guide new medication approaches for people with problem drinking.
Who could benefit from this research
Good fit: Adults who drink heavily or have alcohol use disorder, especially those with reduced sensitivity to alcohol, would be the main group who might benefit from related treatments.
Not a fit: People who are not drinking, are pregnant, have contraindications to PDE4 inhibitors, or whose drinking problems are driven primarily by non-biological factors may not directly benefit from this work.
Why it matters
Potential benefit: Could point to medications that lower alcohol tolerance and reduce heavy drinking in people with alcohol use disorder.
How similar studies have performed: Preclinical rodent studies including work with apremilast have shown reduced alcohol drinking and tolerance, but human trials are limited and translation to people is unproven.
Where this research is happening
AUSTIN, UNITED STATES
- UNIVERSITY OF TEXAS AT AUSTIN — AUSTIN, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: MESSING, ROBERT O. — UNIVERSITY OF TEXAS AT AUSTIN
- Study coordinator: MESSING, ROBERT O.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.