The endocannabinoid 2-arachidonoylglycerol mediates D1 and D2 receptor cooperative enhancement of rat nucleus accumbens core neuron firing.
The endocannabinoid 2-arachidonoylglycerol mediates D1 and D2 receptor cooperative enhancement of rat nucleus accumbens core neuron firing.
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DOI：
10.1016/j.neuroscience.2011.07.055
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发表时间：
2011-10-13
期刊：
影响因子：
3.3
通讯作者：
Hopf, F. W.
中科院分区：
文献类型：
--
作者：
Seif, T.;Makriyannis, A.;Kunos, G.;Bonci, A.;Hopf, F. W.
Many motivated and addiction-related behaviors are sustained by activity of both dopamine D1- and D2-type receptors (D1Rs and D2Rs) as well as CB1 receptors (CB1Rs) in the nucleus accumbens (NAc). Here, we use in vitro whole-cell patch-clamp electrophysiology to describe an endocannabinoid (eCB)–dopamine receptor interaction in adult rat NAc core neurons. D1R and D2R agonists in combination enhanced firing, with no effect of a D1R or D2R agonist alone. This D1R+D2R-mediated firing increase required CB1Rs, since it was prevented by the CB1R antagonists AM251 and Rimonabant. The D1R+D2R firing increase also required phospholipase C (PLC), the major synthesis pathway for the eCB 2-arachidonoylglycerol (2-AG) and one of several pathways for anandamide. Further, inhibition of 2-AG hydrolysis with the monoglyceride lipase (MGL) inhibitor JZL184 allowed subthreshold levels of D1R+D2R receptor agonists to enhance firing, while inhibition of anandamide hydrolysis with the fatty acid amide hydrolase (FAAH) inhibitors URB597 or AM3506 did not. Filling the postsynaptic neuron with 2-AG enabled subthreshold D1R+D2R agonists to increase firing, and the 2AG+D1R+D2R increase in firing was prevented by a CB1R antagonist. Also, the metabotropic glutamate receptor 5 (mGluR5) blocker MPEP prevented the ability of JZL184 to promote subthreshold D1R+D2R enhancement of firing, while the 2-AG+D1R+D2R increase in firing was not prevented by the mGluR5 blocker, suggesting that mGluR5s acted upstream of 2-AG production. Thus, our results taken together are consistent with the hypothesis that NAc core eCBs mediate dopamine receptor (DAR) enhancement of firing, perhaps providing a cellular mechanism underlying the central role of NAc core D1Rs, D2Rs, CB1Rs, and mGluR5s during many drug-seeking behaviors.
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影响因子：
10.6
作者：
Besheer, Joyce;Grondin, Julie J. M.;Cannady, Reginald;Sharko, Amanda C.;Faccidomo, Sara;Hodge, Clyde W.
通讯作者：
Hodge, Clyde W.
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Pierce, RC
DOI：
10.1073/pnas.0706999105
发表时间：
2008-08-26
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
5.3
作者：
Caille, Stephanie;Alvarez-Jaimes, Lily;Parsons, Loren H.
通讯作者：
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