Hyperserotonemia, during the early developmental phase, generates behavioral and biochemical phenotypes associated with
autism spectrum disorder (ASD) in rats. Phosphodiesterase‑1 (PDE1) inhibitors are known to provide benefits in various brain conditions. We investigated the role of a selective PDE1 inhibitor,
vinpocetine on ASD‑related behavioral phenotypes (social behavioral deficits, repetitive behavior, anxiety, and hyperlocomotion) in a developmental hyperserotonemia (DHS) rat model. Also, effects on
biochemical markers related with neuronal function
brain derived neurotrophic factor (
BDNF) and phosphorylated
cAMP response element binding protein (pCREB),
inflammation interleukins (IL‑6 and IL‑10) and
tumor necrosis factor-alpha (TNF‑α), and oxidative stress (
TBARS and GSH) were studied in important brain areas (frontal cortex, cerebellum, hippocampus, and striatum). Administration of 5‑methoxytryptamine (5‑MT) to rats prenatally (gestational day 12) and in early developmental stages postnatal day (PND 0 - PND 20), resulted in impaired behavior and brain biochemistry. Administration of
vinpocetine daily (10 and 20 mg/kg) to 5‑MT rats from PND 21 to PND 48 resulted in an improvement of behavioral deficits. Also,
vinpocetine administration significantly increased the levels of
BDNF, ratio of pCREB/ CREB, IL‑10, and GSH, and significantly decreased TNF‑α, IL‑6, and
TBARS levels in different brain areas. Finally, our correlation analysis indicated that behavioral outcomes were significantly associated with the biochemical outcome.
Vinpocetine, a selective PDE1 inhibitor, rectified important behavioral phenotypes related with ASD, possibly by improving markers of neuronal function,
brain inflammation, and brain oxidative stress. Thus, PDE1 could be a potential target for pharmacological interventions and furthering our understanding of ASD pathogenesis.