© Neuroscience-Net Volume 1, Article #10006

Received June 5, 1996 Accepted for Publication August 7, 1996 Published August 21, 1996

The neuroanatomical distribution of [³H]YM 09151-2 (cis-N-(1-benzyl-2-methylpyrrolidine-3-yl)-5- chloro-2-methoxy-4-methylaminobenzamide; emonapride) was mapped in squirrel monkey (Saimiri sciureus) brain using quantitative receptor autoradiography, and was compared to the neuroanatomical distribution of the dopamine transporter defined with [³H]WIN 35,428 ([³H]CFT) and of dopamine D1 receptors defined with [³H]SCH 23390. Preincubation of caudate-putamen tissue sections increased [³H]YM 09151-2 binding by nearly 70%, suggesting inhibition of radioligand binding by endogenous substances. The pharmacological specificity of [³H]YM 09151-2 binding in caudate-putamen tissue sections was suggestive of binding to dopamine D2-like receptors. Moderate levels of sulpiride-insensitive [³H]YM 09151-2 binding were detected in extrastriatal regions including the medial prefrontal cortex, the septal area, the claustrum, amygdala and the hippocampus. Sulpiride-insensitive [³H]YM 09151-2 binding in hippocampal tissue sections was inhibited in part by the 5-HT1A receptor antagonist NAN-190 and by the 5-HT4 receptor antagonists GR 113808 and SB 204070 suggesting that a portion of sulpiride-insensitive radioligand binding may be to serotonin 5-HT1A and/or 5-HT4 receptors. We conclude that [³H]YM 09151-2 labels non-D2-like receptors that are sulpiride- insensitive in a number of brain regions. This lack of D2-like receptor selectivity combined with our finding that endogenous substances may inhibit YM 09151-2 binding suggest that it may not be optimal as a probe for in vivo brain imaging of dopamine D2-like receptors, and that appropriate masking and baselines must be instituted in in vitro studies. D1 dopamine receptor distribution in squirrel monkey brain closely paralleled distributions reported in prior studies in other primate species. The significance of the differing degrees of colocalization between [³H]YM 09151-2 labeled dopamine D2 receptors, the dopamine transporter and dopamine D1 receptors is discussed.