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Updated: Dec 1, 2025
Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Papaverine ameliorates prenatal alcohol-induced experimental attention deficit hyperactivity disorder by regulating
Niti Sharma1, Neerupma Dhiman2, Lalit K Golani3
1Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India.
Insights
Papaverine, a PDE10A inhibitor, improved ADHD-like behaviors in a prenatal alcohol exposure model. This suggests PDE10A may be a therapeutic target for attention deficit hyperactivity disorder.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder.
- Phosphodiesterase10A (PDE10A) inhibition shows promise for brain conditions.
Purpose of the Study:
- To investigate papaverine, a PDE10A inhibitor, for ADHD phenotypes in a prenatal alcohol exposure (PAE) model.
- To explore underlying mechanisms by examining protein markers of neuronal function, inflammation, and oxidative stress.
Main Methods:
- Prenatal alcohol exposure (PAE) model in animals to induce ADHD-like behaviors.
- Behavioral assessments using open-field, y-maze, and elevated plus maze tests.
- Analysis of protein markers (BDNF, pCREB, IL-6, IL-10, TNF-α, TBARS, GSH) in brain regions.
Main Results:
- Papaverine administration ameliorated hyperactivity, inattention, and anxiety in PAE animals.
- Papaverine increased BDNF, pCREB, IL-10, and GSH levels.
- Papaverine decreased TNF-α, IL-6, and TBARS levels in the brain.
Conclusions:
- Papaverine, a PDE10A inhibitor, effectively treated ADHD-like behaviors in the PAE model.
- The therapeutic effects are likely mediated by modulating neuronal survival, transcription factors, inflammation, and oxidative stress.
- PDE10A inhibition represents a potential therapeutic strategy for ADHD.
Abstract:
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Phosphodiesterase10A (PDE10A) has been shown to provide benefits in various brain conditions. We investigated the role of papaverine, a selective PDE10A inhibitor on core phenotypes in prenatal alcohol exposure (PAE) model of ADHD. In order to identify probable mechanisms involved, the effects on several protein markers of neuronal function such as, neuronal survival-BDNF, neuronal transcription factor-pCREB, brain inflammation (IL-6, IL-10, and TNF-α), and brain oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, and striatum. PAE resulting hyper-locomotion, inattention, and anxiety were studied by the use of open-field, y-maze, and elevated plus maze, respectively. Administration of papaverine (15/30 mg kg-1 ) to PAE group of animals resulted in amelioration of hyperactivity, inattention, and anxiety. Also, papaverine resulted in significant increase of the levels in BDNF, pCREB, IL-10, and GSH along with significant decrease of TNF-α, IL-6, and TBARS in different brain areas of PAE group. Papaverine, a selective PDE10A inhibitor rectified behavioural phenotypes associated with ADHD, possibly by altering the protein markers associated with neuronal survival, neuronal transcription factor, brain inflammation, and brain oxidative stress. Implicating PDE10A as a possible target for furthering our understanding of ADHD phenotypes.
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