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Published on: March 17, 2019
Early administration of tiapride to young rats without long-lasting changes in the development of the dopaminergic
Nathalie Bock1, Gunther H Moll, Maike Wicker
1Department of Child and Adolescent Psychiatry, University of Göttingen, Germany.
Insights
Tiapride, used for tic disorders, shows no lasting effects on the developing brain
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Tiapride is a dopamine D2/D3 antagonist used for pediatric tic disorders and stuttering.
- Clinical safety is established, but effects on brain development remain unclear.
- Investigating tiapride's impact on the dopaminergic system is crucial for pediatric treatment.
Purpose of the Study:
- To investigate the long-term effects of tiapride on the developing dopaminergic system in rats.
- To assess dopaminergic activity parameters after early and late tiapride administration.
- To provide essential data for safe pediatric drug treatment.
Main Methods:
- Rats received tiapride (30 mg/kg/day) in drinking water during pre- and post-pubertal stages.
- Dopamine transporter and D2 receptor densities were measured using ligand-binding assays.
- Dopamine, DOPAC, and HVA levels in the striatum were quantified via HPLC.
Main Results:
- Tiapride administration did not alter dopamine transporter or D2 receptor density long-term.
- A temporary reduction in D2 receptor binding, dopamine, and DOPAC was observed during treatment.
- No persistent changes in the central dopaminergic system were detected post-treatment.
Conclusions:
- Tiapride treatment does not induce lasting alterations in the developing central dopaminergic system.
- Findings support the clinical safety of tiapride in children.
- Further research can inform optimal pediatric therapeutic strategies.
Background:
The benzamide tiapride, a selective dopamine D2/D3-receptor antagonist, can be used effectively in children to treat tic disorders and stuttering. Tiapride is a clinically safe substance (even during long-term treatment and when given to young children). Unfortunately, its probable effects on general brain development and the maturation of the dopaminergic system have not been investigated. Thus, important information for drug treatment in children is missing. Therefore, this study in rats describes tiapride's effects on several parameters of dopaminergic activity (dopamine transporter, D2 receptor, dopamine, DOPAC, and homovanillic acid in the striatum) seen after tiapride administration (30 mg/kg/day) to prepubertal (from day 25-39) and postpubertal (from day 50-64) rats.
Methods:
Three groups of rats (n = 6) received tiapride within their drinking water for 14 days. Two groups were treated before puberty; one of those was killed at day 50, the other at day 90. The group treated after puberty was measured at day 90. A fourth group (n = 6) was treated from day 50 to day 53 and measured under tiapride at day 53. Changes were measured by ligand-binding assays (KD and Bmax values of dopamine transporter by [3H]-GBR binding and D2 receptor by [3H]- spiperone binding) and by HPLC (concentrations of dopamine, DOPAC, and homovanillic acid).
Results:
The density of dopamine transporters and D2 receptors remained unaffected after early (day 25) and late (day 50) tiapride administration. Only during the treatment period could a significant reduction of D2-receptor binding (displacement of spiperone) and of dopamine and DOPAC levels be stated.
Conclusions:
These data suggest that tiapride treatment during postnatal brain development causes no long-lasting changes in the development of the central dopaminergic system and is in line with clinical experience in children.
