alpha 2-Adrenergic Drugs Modulate the Binding of [F-18]Fallypride to Dopamine D-2/3 Receptors in Striatum of Living Mouse

作者：Rominger Axel^*; Mille Erik; Boning Guido; Wangler Bjorn; Gildehaus Franz Josef; Arszol Cornelia; Bartenstein Peter; Cumming Paul

来源：Synapse, 2010, 64(8): 654-657.

DOI：10.1002/syn.20785

• dopamine D-2/3 receptor
• fallypride
• microPET
• alpha 2 antagonist
• mouse brain

Aim. To test for alpha(2) adrenergic modulation of dopamine D-2/3 receptor availability in striatum of living mice using the high-affinity ligand [F-18]fallypride and microPET Methods. Groups of anesthetized mice were pretreated with saline, the alpha(2)-agonist clonidine (1 mg/kg), and the alpha(2)-antagonists RX821002 (1 mg/kg) and yohimbine (1 mg/kg). Dynamic microPET recordings lasting 120 mm were then initiated upon v. tracer injection of [F-18]fallypride Parametric maps of [F-18]fallypride binding potential (BPND) were calculated using the Logan method, with cerebellum serving as the reference region Results. Mean striatal [F-18]fallypride BPND was 10.6 +/- 1.7 in the saline control animals, 8.9 +/- 1 7 (-16%; P < 0.05) in the RX821002 group, 8.3 +/- 2.6 (-22%; P < 0.05) in the yohimbine group and 10.3 +/- 2 2 (n s) in the clonidine group. Conclusions. These findings are consistent with a tonic inhibition of dopamine release by alpha(2) adrenergic receptors, such that a, blockade increased the competition from endogenous dopamine at D-2/3 receptors, thus reducing the [F-18]fallypride BPND by about 20%. Absent effects of clonidine suggest a ceiling effect in the tonic inhibition of dopamine release. This in vivo PET evidence for alpha(2)/dopaminergic interaction may be relevant to putative actions of atypical antipsychotic medications via adrenergic receptors. Synapse 64:654-657, 2010.

• 出版日期2010-8