TY - JOUR
T1 - Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases
AU - Wei, Feng
AU - Qiu, Chang Shen
AU - Kim, Susan J.
AU - Muglia, Lisa
AU - Maas, James W.
AU - Pineda, Victor V.
AU - Xu, Hai Ming
AU - Chen, Zhou Feng
AU - Storm, Daniel R.
AU - Muglia, Louis J.
AU - Zhuo, Min
N1 - Funding Information:
We thank Drs. E.R. Kandel, S.A. Siegelbaum, and Kenneth Blum for helpful discussions and suggestion of rescue experiments, and the members of Zhuo lab for their comments and advice on the manuscript. This work was supported in part by grants from the NIH (NIDA, NINDS, M.Z.; NIA to L.J.M.) and the McDonnell Center for Higher Brain Function at Washington University (to L.J.M. and M.Z.).
PY - 2002/11/14
Y1 - 2002/11/14
N2 - Adenylyl cyclase types 1 (AC1) and 8 (AC8), the two major calmodulin-stimulated adenylyl cyclases in the brain, couple NMDA receptor activation to cAMP signaling pathways. Cyclic AMP signaling pathways are important for many brain functions, such as learning and memory, drug addiction, and development. Here we show that wild-type, AC1, AC8, or AC1&8 double knockout (DKO) mice were indistinguishable in tests of acute pain, whereas behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant, were reduced or abolished in AC1&8 DKO mice. AC1 and AC8 are highly expressed in the anterior cingulate cortex (ACC), and contribute to inflammation-induced activation of CREB. Intra-ACC administration of forskolin rescued behavioral allodynia defective in the AC1&8 DKO mice. Our studies suggest that AC1 and AC8 in the ACC selectively contribute to behavioral allodynia.
AB - Adenylyl cyclase types 1 (AC1) and 8 (AC8), the two major calmodulin-stimulated adenylyl cyclases in the brain, couple NMDA receptor activation to cAMP signaling pathways. Cyclic AMP signaling pathways are important for many brain functions, such as learning and memory, drug addiction, and development. Here we show that wild-type, AC1, AC8, or AC1&8 double knockout (DKO) mice were indistinguishable in tests of acute pain, whereas behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant, were reduced or abolished in AC1&8 DKO mice. AC1 and AC8 are highly expressed in the anterior cingulate cortex (ACC), and contribute to inflammation-induced activation of CREB. Intra-ACC administration of forskolin rescued behavioral allodynia defective in the AC1&8 DKO mice. Our studies suggest that AC1 and AC8 in the ACC selectively contribute to behavioral allodynia.
UR - http://www.scopus.com/inward/record.url?scp=18744396642&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(02)01019-X
DO - 10.1016/S0896-6273(02)01019-X
M3 - Article
C2 - 12441059
AN - SCOPUS:18744396642
SN - 0896-6273
VL - 36
SP - 713
EP - 726
JO - Neuron
JF - Neuron
IS - 4
ER -