Development of 5-HT transporter density and long-term effects of methylphenidate in an animal model of ADHD.
Although stimulants as the treatment of choice are widely prescribed in ADHD, little is known about their long-term neurobiological effects. Hence, for the first time the present study examined the long-term effects of chronic methylphenidate (MPH) administration on striatal 5-hydroxytryptamine transporter (5-HTT) densities in an animal model of ADHD. First, it compared the normal development of striatal 5-HTT densities of spontaneously hypertensive rats (SHR) as an animal model of ADHD and Wistar Kyoto (WKY) rats as controls; binding of the highly selective ligand of 5-HTT [(3)H]paroxetine was determined on membrane preparations of the striatum of SHR and WKY rats on postnatal days 25, 50, and 90, i.e. from the time of weaning until adulthood. Second, the long-term effect of chronic administration of 2 mg/kg per day MPH at two different developmental stages (days 25-39 or 50-64) on the striatal 5-HTT density was examined in both rat strains at day 90. Long-term effects of MPH treatment on striatal 5-HTT density in adulthood could be ruled out in both healthy (WKY) and "ADHD" rats (SHR). But a higher striatal 5-HTT density in older SHR versus WKY rats might indicate ADHD specific changes in the 5-HT system that needs further investigation not only in animals.
Roessner
Veit
V
Department of Child and Adolescent Psychiatry, University of Goettingen, Goettingen, Germany.
Manzke
Till
T
Becker
Andreas
A
Rothenberger
Aribert
A
Bock
Nathalie
N
D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D002352:Carrier Proteins / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008774:Methylphenidate / Q000633:toxicity*; D017374:Paroxetine / Q000493:pharmacokinetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011955:Receptors, Drug / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D017374:Paroxetine; D011955:Receptors, Drug; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat; C092604:paroxetine receptor