Binding of [123I]iodobenzamide to the rat D2 receptor after challenge with various doses of methylphenidate: an in vivo imaging study with dedicated small animal SPECT.
OBJECTIVE
The effect of various doses of methylphenidate on the binding of [(123)I]iodobenzamide ([(123)I]IBZM) to the rat D(2) receptor was assessed using small animal SPECT.


METHODS
D(2) receptor binding was measured at baseline and after pretreatment with various doses of methylphenidate. For baseline and methylphenidate challenge, striatal equilibrium ratios (V(3)″) were computed as an estimation of the binding potential.


RESULTS
After methylphenidate, striatal V(3)″ was 1.61 ± 0.61 (mean ± SD; 0.3 mg/kg), 0.91 ± 0.44 (3 mg/kg), 1.01 ± 0.44 (10 mg/kg), 0.91 ± 0.34 (30 mg/kg) and 0.99 ± 0.51 (60 mg/kg). Baseline values amounted to 1.73 ± 0.48, 1.32 ± 0.35, 1.50 ± 0.27, 1.82 ± 0.55 and 1.66 ± 0.41, respectively. Differences between baseline and methylphenidate were significant for the doses 3, 10, 30 and 60 mg/kg, whereas no significant difference was obtained for 0.3 mg/kg methylphenidate. Between-group differences of percentage reduction of D(2) receptor binding were only significant for the groups pretreated with 0.3 and 30 mg/kg methylphenidate, respectively.


CONCLUSIONS
Methylphenidate between 0.3 and 60 mg/kg decreased D(2) receptor binding with a maximum reduction after 30 mg/kg. As no between-group differences were evident between the groups pretreated with 3, 10, 30 and 60 mg/kg, it may be inferred that doses ≥ 3 mg/kg were sufficient to induce maximum dopamine concentration in the synaptic cleft. Further investigations are needed in order to clarify whether the variation between subjects can be accounted for by different synaptic mechanisms at the presynaptic binding site.
Clinic of Nuclear Medicine, University Hospital Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. Susanne.Nikolaus@uni-duesseldorf.de
Susanne
S
Nikolaus
Christina
C
Antke
Markus
M
Beu
Konstantin
K
Kley
Andreas
A
Wirrwar
Joseph P
JP
Huston
Hans-Wilhelm
HW
Müller
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007462:Iodobenzenes / Q000378:metabolism*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D007462:Iodobenzenes; D017448:Receptors, Dopamine D2; C426805:idobenzamide; D008774:Methylphenidate; D004298:Dopamine