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Increased desensitization of dopamine D(2) receptor-mediated response in the ventral tegmental area in the absence of adenosine A(2A) receptors.

Al-Hasani, R, Foster, JD, Metaxas, A, Ledent, C, Hourani, SM, Kitchen, I and Chen, Y (2011) Increased desensitization of dopamine D(2) receptor-mediated response in the ventral tegmental area in the absence of adenosine A(2A) receptors. Neuroscience, 190. pp. 103-111.

Electrophysiology_paper_revised 8-6-11-yc.pdf - Accepted version Manuscript
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G-protein coupled receptors interact to provide additional regulatory mechanisms for neurotransmitter signaling. Adenosine A(2A) receptors are expressed at a high density in striatal neurons, where they closely interact with dopamine D(2) receptors and modulate effects of dopamine and responses to psychostimulants. A(2A) receptors are expressed at much lower densities in other forebrain neurons but play a more prominent yet opposing role to striatal receptors in response to psychostimulants in mice. It is, therefore, possible that A(2A) receptors expressed at low levels elsewhere in the brain may also regulate neurotransmitter systems and modulate neuronal functions. Dopamine D(2) receptors play an important role in autoinhibition of neuronal firing in dopamine neurons of the ventral tegmental area (VTA) and dopamine release in other brain areas. Here, we examined the effect of A(2A) receptor deletion on D(2) receptor-mediated inhibition of neuronal firing in dopamine neurons in the VTA. Spontaneous activity of dopamine neurons was recorded in midbrain slices, and concentration-dependent effects of the dopamine D(2) receptor agonist, quinpirole, was compared between wild-type and A(2A) knockout mice. The potency of quinpirole applied in single concentrations and the expression of D(2) receptors were not altered in the VTA of the knockout mice. However, quinpirole applied in stepwise escalating concentrations caused significantly reduced maximal inhibition in A(2A) knockout mice, indicating an enhanced agonist-induced desensitization of D(2) receptors in the absence of A(2A) receptors. The A(2A) receptor agonist, CGS21680, did not exert any effect on dopamine neuron firing or response to quinpirole, revealing a novel non-pharmacological interaction between adenosine A(2A) receptors and dopaminergic neurotransmission in midbrain dopamine neurons. Altered D(2) receptor desensitization may result in changes in dopamine neuron firing rate and pattern and dopamine release in other brain areas in response to persistent dopamine release and administration of psychostimulants.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
Al-Hasani, R
Foster, JD
Metaxas, A
Ledent, C
Hourani, SM
Kitchen, I
Chen, Y
Date : 5 September 2011
DOI : 10.1016/j.neuroscience.2011.05.068
Additional Information : NOTICE: this is the author’s version of a work that was accepted for publication in Neuroscience. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuroscience, 190, September 2011, DOI 10.1016/j.neuroscience.2011.05.068.
Depositing User : Symplectic Elements
Date Deposited : 02 Dec 2011 16:06
Last Modified : 31 Oct 2017 14:10

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