Binding of [^sup 123^I]iodobenzamide to the rat D^sub 2^ receptor after challenge with various doses of methylphenidate: an in vivo imaging study with dedicated small animal SPECT

• Published in: European journal of nuclear medicine and molecular imaging 2011-04, Vol.38 (4), p.694
• Main Authors: Nikolaus, Susanne, Antke, Christina, Beu, Markus, Kley, Konstantin, Wirrwar, Andreas, Huston, Joseph P, Müller, Hans-wilhelm
• Format: Article
• Language: English
• Subjects: Binding sites; Drug therapy; Medical imaging; Neurons; Rodents
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-010-1668-x

The effect of various doses of methylphenidate on the binding of [^sup 123^I]iodobenzamide ([^sup 123^I]IBZM) to the rat D^sub 2^ receptor was assessed using small animal SPECT. D^sub 2^ receptor binding was measured at baseline and after pretreatment with various doses of methylphenidate. For baseline and methylphenidate challenge, striatal equilibrium ratios (V^sub 3^'') were computed as an estimation of the binding potential. After methylphenidate, striatal V^sub 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^sub 2^ receptor binding were only significant for the groups pretreated with 0.3 and 30 mg/kg methylphenidate, respectively. Methylphenidate between 0.3 and 60 mg/kg decreased D^sub 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.[PUBLICATION ABSTRACT]