Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice.
Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice.
复制标题
DOI：
10.1177/02698811221132214
复制
发表时间：
2022-11
影响因子：
4.1
通讯作者：
Damaj, M. Imad
中科院分区：
文献类型：
--
作者：
Akinola, Lois S.;Bagdas, Deniz;Alkhlaif, Yasmin;Jackson, Asti;Gurdap, Cenk O.;Rahimpour, Elnaz;Carroll, F. Ivy;Papke, Roger L.;Damaj, M. Imad
Because of their implications in several pathological conditions, α4β2* nicotinic acetylcholine receptors (nAChRs) are potential targets for the treatment of nicotine dependence, pain, and many psychiatric and neurodegenerative diseases. However, they exist in various subtypes, and finding selective tools to investigate them has proved challenging. The nicotinic receptor agonist, 5-iodo-A-85380, has helped in delineating the function of β2-containing subtypes in vitro; however, much is still unknown about its behavioral effects. Furthermore, its effectiveness on α6-containing subtypes are limited. To investigate the effects of 5-iodo-A-85380 on nociception (formalin, hot-plate, and tail-flick tests), locomotion, hypothermia, and conditioned reward after acute and repeated administration, and to examine the potential role of β2 and α6 nAChR subunits in these effects. Lastly, we describe its selectivity for expressed low-sensitivity and high-sensitivity α4β2 receptors. 5-iodo-A-85380 dose-dependently induced hypothermia, locomotion suppression, conditioned place preference, and antinociception (only in the formalin test but not in the hot plate or tail-flick tests). Furthermore, these effects were mediated by β2 and not α6 nicotinic subunits. Finally, we show that 5-iodo-A-85380 potently activates both stoichiometries of α4β2 nAChRs with different efficacies, being a full agonist on high-sensitivity α4(2)β2(3) nAChRs, and a partial agonist on low-sensitivity α4(3)β2(2) nAChRs and α6-containing subtypes as well. This research was supported by the National Institutes of Health grants GM57481 to RLP and DA005274 and DA032246 to MID. Lois Akinola was supported in part by the T32 DA007027/DA/NIDA and the NIH IMSD training grant R25GM090084. The authors declare no conflicts of interest.
登录
查看更多内容
影响因子：
1.6
作者：
Fowler CD;Arends MA;Kenny PJ
通讯作者：
Kenny PJ
DOI：
10.5402/2012/170981
发表时间：
2012
期刊：
ISRN pharmacology
影响因子：
--
作者：
Umezu T
通讯作者：
Umezu T
影响因子：
7.3
作者：
Koren, AO;Horti, AG;London, ED
通讯作者：
London, ED
影响因子：
5.8
作者：
Gotti, Cecilia;Clementi, Francesco;Zoli, Michele
通讯作者：
Zoli, Michele
影响因子：
3.4
作者：
Jareczek, Francis J.;White, Stephanie R.;Hammond, Donna L.
通讯作者：
Hammond, Donna L.