Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action.

Abstract:

:Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked mu, delta, and kappa opioid receptors. One major effector for these receptors is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the ten known forms of adenylyl cyclase are involved in mediating opioid actions. Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum. Furthermore, the behavioral effects of selective mu or delta opioid receptor agonists are lost in AC5-/- mice, whereas the behavioral effects of selective kappa opioid receptor agonists are unaffected. These behavioral data are consistent with the observation that the ability of a mu or delta opioid receptor agonist to suppress adenylyl cyclase activity was absent in striatum of AC5-/- mice. Together, these results establish AC5 as an important component of mu and delta opioid receptor signal transduction mechanisms in vivo and provide further support for the importance of the cAMP pathway as a critical mediator of opioid action.

authors

Kim KS,Lee KW,Lee KW,Im JY,Yoo JY,Kim SW,Lee JK,Nestler EJ,Han PL

doi

10.1073/pnas.0508812103

keywords:

subject

Has Abstract

pub_date

2006-03-07 00:00:00

pages

3908-13

issue

10

eissn

0027-8424

issn

1091-6490

pii

0508812103

journal_volume

103

pub_type

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