nACfiR upregulation by ciironic exposure to nicotine and ottier nicotinic drugs The Overall Progress Report and Overall Description sections provide the logic and background for the study of receptor upregulation by candidate drugs. Upregulation in 2 pathways related to nicotine addiction Cellular and circuit-level research on nAChRs is governed by the fact that only a handful of papers present believable eEPSCs, sEPSCs, or mEPSCs associated with nAChR activation by ACh in the brain. Investigators believe that most HS nicotinic receptors are on presynaptic terminals, where they control transmitter release (and therefore pose challenges for detailed study) (MacDermott et al., 1999). Many studies also reveal the presence of somatodendritic HS nAChRs (mostly a4B2* and a6*). Little or no evidence shows that these somatodendritic receptors respond to circulating or released ACh. But there is much evidence that these nAChRs do respond to nicotine with both activation and, in some cases, desensitization, primarily because nicotine is not hydrolyzed by acetylcholinesterase.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19DA019375-09
Application #
8534075
Study Section
Special Emphasis Panel (ZMH1-ERB-C)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
9
Fiscal Year
2013
Total Cost
$250,546
Indirect Cost
$95,888
Name
California Institute of Technology
Department
Type
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon et al. (2014) Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function ?6* nAChRs. J Neurochem 129:315-27
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