Early administration of tiapride to young rats without long-lasting changes in the development of the dopaminergic system.
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.
Department of Child and Adolescent Psychiatry, University of Göttingen, Germany.
Nathalie
N
Bock
Gunther H
GH
Moll
Maike
M
Wicker
Jürgen
J
Pilz
Eckart
E
Rüther
Tobias
T
Banaschewski
Gerald
G
Huether
Aribert
A
Rothenberger
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D006719:Homovanillic Acid / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013134:Spiperone / Q000493:pharmacokinetics; D013976:Tiapamil Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D013976:Tiapamil Hydrochloride; D004298:Dopamine; D006719:Homovanillic Acid