TY - JOUR T1 - Impaired D2 Dopamine Receptor Function in Mice Lacking Type 5 Adenylyl Cyclase JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7931 LP - 7940 DO - 10.1523/JNEUROSCI.22-18-07931.2002 VL - 22 IS - 18 AU - Ko-Woon Lee AU - Jang-Hee Hong AU - In Young Choi AU - Yongzhe Che AU - Ja-Kyeong Lee AU - Sung-Don Yang AU - Chang-Woo Song AU - Ho Sung Kang AU - Jae-Heun Lee AU - Jai Sung Noh AU - Hee-Sup Shin AU - Pyung-Lim Han Y1 - 2002/09/15 UR - http://www.jneurosci.org/content/22/18/7931.abstract N2 - Dopamine receptor subtypes D1 and D2, and many other seven-transmembrane receptors including adenosine receptor A2A, are colocalized in striatum of brain. These receptors stimulate or inhibit adenylyl cyclases (ACs) to produce distinct physiological and pharmacological responses and interact with each other synergistically or antagonistically at various levels. The identity of the AC isoform that is coupled to each of these receptors, however, remains unknown. To investigate the in vivo role of the type 5 adenylyl cyclase (AC5), which is preferentially expressed in striatum, mice deficient for the AC5 gene were generated. The genetic ablation of the AC5 gene eliminated >80% of forskolin-induced AC activity and 85–90% of AC activity stimulated by either D1 or A2A receptor agonists in striatum. However, D1- or A2A-specific pharmaco-behaviors were basically preserved, whereas the signal cascade from D2 to AC was completely abolished inAC5−/−, and motor activity of AC5−/− was not suppressed by treatment of cataleptic doses of the antipsychotic drugs haloperidol and sulpiride. Interestingly, both haloperidol and clozapine at low doses remarkably increased the locomotion ofAC5−/− in the open field test that was produced in part by a common mechanism that involved the increased activation of D1 dopamine receptors. Together, these results suggest that AC5 is the principal AC integrating signals from multiple receptors including D1, D2, and A2A in striatum and the cascade involving AC5 among diverse D2 signaling pathways is essential for neuroleptic effects of antipsychotic drugs. ER -