Mu-opioid receptor and CREB activation are required for nicotine reward.

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Walters CL, Cleck JN, Kuo YC, Blendy JA

Mu-opioid receptor and CREB activation are required for nicotine reward.

Neuron. 2005 Jun 16;46(6):933-43.

PubMed ID

15953421 [ View in PubMed

]

Abstract

Environmental cues associated with nicotine delivery are an important part of the stimulus that sustains smoking behavior and is often coupled with craving and relapse; however, the neuronal circuitry and molecular substrates underlying this process are still poorly understood. Exposure to an environment previously associated with rewarding properties of nicotine results in an increase of CREB phosphorylation similar to that seen following nicotine administration, and this response is absent in MOR(-/-) mice. Moreover, a single administration of an opioid receptor antagonist, naloxone, blocks both the conditioned molecular response (CREB phosphorylation) and the conditioned behavioral response (nicotine reward) in a place preference paradigm. Lastly, repeated nicotine administration results in increased expression of MORs. However, this effect, along with rewarding properties of nicotine, is blocked in mice with a targeted disruption in the CREB gene. Together, pharmacologic and genetic manipulations indicate that phosphorylation of CREB and upregulation of functional MORs are required for nicotine-conditioned reward.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Naloxone	Cyclic AMP-responsive element-binding protein 1	Protein	Humans	No	Other/unknown	Details