JN AJP: Heart and Circulatory Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

J Neurophysiol (December 22, 2004). doi:10.1152/jn.00855.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
93/6/3086    most recent
00855.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Margolis, E. B.
Right arrow Articles by Fields, H. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Margolis, E. B.
Right arrow Articles by Fields, H. L.
Submitted on August 18, 2004
Accepted on December 17, 2004

Both Kappa and Mu Opioid Agonists Inhibit Glutamatergic Input to Ventral Tegmental Area Neurons

Elyssa B. Margolis1*, Gregory O. Hjelmstad2, Antonello Bonci2, and Howard L. Fields2

1 Ernest Gallo Clinic & Research Center, University of California, San Francisco, Emeryville, CA, USA
2 Ernest Gallo Clinic & Research Center, University of California, San Francisco, Emeryville, CA, USA; Neurology, University of California, San Francisco, San Francisco, CA, USA; Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: elyssam{at}egcrc.net.

The ventral tegmental area (VTA) plays a critical role in motivation and reinforcement. Kappa and mu opioid receptor (KOP-R and MOP-R) agonists microinjected into the VTA produce powerful and largely opposing motivational actions. There are several classes of neuron in the VTA: principal, secondary, and tertiary. Glutamate transmission within the VTA contributes to the motivational effects of opioids. Therefore, information about opioid control of glutamate release onto each class of VTA neuron is important. To address this issue we performed whole cell patch-clamp recordings in VTA slices and measured excitatory postsynaptic currents (EPSCs) in all types of VTA neurons. The KOP-R agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U69593; 1 µM) produced a small reduction in EPSC amplitude in principal neurons (14%), and a significantly larger inhibition in secondary (47%) and tertiary (33%) neurons. The MOP-R agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-Enkephalin (DAMGO; 3 µM) inhibited glutamate release in principal (42%), secondary (45%) and tertiary neurons (35%). Unlike principal and tertiary neurons, in secondary neurons the magnitude of the U69593 EPSC inhibition was positively correlated with that produced by DAMGO. Finally, DAMGO did not occlude the U69593 effect in principal neurons, suggesting that some glutamatergic terminals are independently controlled by KOP and MOP receptor activation. These findings demonstrate that MOP- and KOP-R agonists regulate excitatory input onto each VTA cell type.




This article has been cited by other articles:


Home page
 J. Neurophysiol.Home page
H. D. Mansvelder
Yin and Yang of VTA Opioid Signaling. Focus on "Both Kappa and Mu Opioid Agonists Inhibit Glutamatergic Input to Ventral Tegmental Area Neurons"
J Neurophysiol, June 1, 2005; 93(6): 3046 - 3047.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2004 by the The American Physiological Society.