Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases

Feng Wei; Chang Shen Qiu; Susan J Kim; Lisa Muglia; James W Maas; Victor V Pineda; Hai Ming Xu; Zhou Feng Chen; Daniel R Storm; Louis J Muglia; Min Zhuo

doi:10.1016/s0896-6273(02)01019-x

Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases

Neuron. 2002 Nov 14;36(4):713-26. doi: 10.1016/s0896-6273(02)01019-x.

Authors

Feng Wei¹, Chang Shen Qiu, Susan J Kim, Lisa Muglia, James W Maas, Victor V Pineda, Hai Ming Xu, Zhou Feng Chen, Daniel R Storm, Louis J Muglia, Min Zhuo

Affiliation

¹ Department of Anesthesiology, Washington University Pain Center, Washington University, St. Louis, MO 63108, USA.

PMID: 12441059
DOI: 10.1016/s0896-6273(02)01019-x

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adenylyl Cyclases / deficiency*
Adenylyl Cyclases / genetics
Animals
Behavior, Animal / physiology
Brain / enzymology*
Brain / physiopathology
Calmodulin / metabolism*
Cyclic AMP / analogs & derivatives
Cyclic AMP / metabolism*
Cyclic AMP Response Element-Binding Protein / metabolism
Enzyme Inhibitors / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Freund's Adjuvant
Hyperalgesia / enzymology
Hyperalgesia / genetics*
Hyperalgesia / physiopathology
Male
Mice
Mice, Knockout
Neural Pathways / enzymology*
Neural Pathways / physiopathology
Pain / enzymology
Pain / genetics*
Pain / physiopathology
Pain Measurement
RNA, Messenger / metabolism
Receptors, N-Methyl-D-Aspartate / metabolism

Substances

Calmodulin
Cyclic AMP Response Element-Binding Protein
Enzyme Inhibitors
Excitatory Amino Acid Antagonists
RNA, Messenger
Receptors, N-Methyl-D-Aspartate
Freund's Adjuvant
Cyclic AMP
Adenylyl Cyclases
adenylyl cyclase 1
adenylyl cyclase 8