Differential Contributions of Prefrontal and Hippocampal Dopamine D 1 and D 2 Receptors in Human Cognitive Functions

• Published in: The Journal of neuroscience Vol. 28; no. 46; pp. 12032 - 12038
• Main Authors: Takahashi, Hidehiko, Kato, Motoichiro, Takano, Harumasa, Arakawa, Ryosuke, Okumura, Masaki, Otsuka, Tatsui, Kodaka, Fumitoshi, Hayashi, Mika, Okubo, Yoshiro, Ito, Hiroshi, Suhara, Tetsuya
• Format: Journal Article
• Language: English
• Published: 12.11.2008
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3446-08.2008

Dopamine D 1 receptors in the prefrontal cortex (PFC) are important for prefrontal functions, and it is suggested that stimulation of prefrontal D 1 receptors induces an inverted U-shaped response, such that too little or too much D 1 receptor stimulation impairs prefrontal functions. Less is known of the role of D 2 receptors in cognition, but previous studies showed that D 2 receptors in the hippocampus (HPC) might play some roles via HPC–PFC interactions. We measured both D 1 and D 2 receptors in PFC and HPC using positron emission tomography in healthy subjects, with the aim of elucidating how regional D 1 and D 2 receptors are differentially involved in frontal lobe functions and memory. We found an inverted U-shaped relation between prefrontal D 1 receptor binding and Wisconsin Card Sorting Test performance. However, prefrontal D 2 binding has no relation with any neuropsychological measures. Hippocampal D 2 receptor binding showed positive linear correlations not only with memory function but also with frontal lobe functions, but hippocampal D 1 receptor binding had no association with any memory and prefrontal functions. Hippocampal D 2 receptors seem to contribute to local hippocampal functions (long-term memory) and to modulation of brain functions outside HPC (“frontal lobe functions”), which are mainly subserved by PFC, via the HPC–PFC pathway. Our findings suggest that orchestration of prefrontal D 1 receptors and hippocampal D 2 receptors might be necessary for human executive function including working memory.