GPR88 in A 2A R Neurons Enhances Anxiety-Like Behaviors
GPR88 is an orphan G-protein-coupled receptor highly expressed in striatal dopamine D 1 (receptor) R- and D2R-expressing medium spiny neurons. This receptor is involved in activity and motor responses, and we previously showed that this receptor also regulates anxiety-like behaviors. To determine wh...
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Veröffentlicht in: | eNeuro 2016-07, Vol.3 (4), p.ENEURO.0202-16.2016 |
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Sprache: | eng |
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Zusammenfassung: | GPR88 is an orphan G-protein-coupled receptor highly expressed in striatal dopamine D
1
(receptor) R- and D2R-expressing medium spiny neurons. This receptor is involved in activity and motor responses, and we previously showed that this receptor also regulates anxiety-like behaviors. To determine whether GPR88 in D2R-expressing neurons contributes to this emotional phenotype, we generated conditional
Gpr88
knock-out mice using adenosine A
2A
R (A
2A
R)-Cre-driven recombination, and compared anxiety-related responses in both total and
A
2A
R
-
Gpr88
KO mice.
A
2A
R
-
Gpr88
KO mice showed a selective reduction of
Gpr88
mRNA in D2R-expressing, but not D
1
R-expressing, neurons. These mutant mice showed increased locomotor activity and decreased anxiety-like behaviors in light/dark and elevated plus maze tests. These phenotypes were superimposable on those observed in total
Gpr88
KO mice, demonstrating that the previously reported anxiogenic activity of GPR88 operates at the level of A
2A
R-expressing neurons. Further,
A
2A
R
-
Gpr88
KO mice showed no change in novelty preference and novelty-suppressed feeding, while these responses were increased and decreased, respectively, in the total
Gpr88
KO mice. Also,
A
2A
R
-
Gpr88
KO mice showed intact fear conditioning, while the fear responses were decreased in total
Gpr88
KO. We therefore also show for the first time that GPR88 activity regulates approach behaviors and conditional fear; however, these behaviors do not seem mediated by receptors in A
2A
R neurons. We conclude that
Gpr88
expressed in A
2A
R neurons enhances ethological anxiety-like behaviors without affecting conflict anxiety and fear responses. |
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ISSN: | 2373-2822 2373-2822 |
DOI: | 10.1523/ENEURO.0202-16.2016 |