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Attenuation of DOI‐induced head twitches in mGluR2 KO mice
Author(s) -
Benvenga Mark Joseph,
Chaney Stephen F.,
Baez Melvin,
Britton Thomas C.,
Hornback William J.,
Monn James A.,
Marek Gerard J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a246
Subject(s) - metabotropic glutamate receptor 2 , agonist , metabotropic glutamate receptor , metabotropic receptor , chemistry , glutamate receptor , autoreceptor , stimulation , receptor , pharmacology , medicine , neuroscience , biology , biochemistry
There is substantial pharmacological evidence that glutamate can modulate the effects of 5‐hydroxytryptamine 2A (5‐HT 2A ) receptor activation through stimulation of metabotropic glutamate2/3 receptors (mGluR2/3) in the cerebral cortex. In this work, we show that deletion of mGluR2 profoundly attenuates the head twitch behavior elicited by 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) administration in mice. MGlu2 KO and age‐matched ICR (CD‐1) WT mice (N=8/dose) were administered DOI and observed for head twitch activity over 30 minutes. Additional CD‐1 mice were administered the mGluR2/3 agonist LY379268 or the mGluR2 potentiator LY566332 followed by DOI, and observed for head twitches for 30 minutes. The results indicated that both LY379268 and LY566332 were able to reduce head twitches in a dose‐dependent manner. More importantly, DOI (3mg/kg) failed to elicit head twitches in the mGlu2 KO mice where even a 30 mg/kg dose produced a head shake frequency only ~ 25% of that seen in WT mice. These results indicate that the mGluR2 receptor is intimately involved in modulating head twitches elicited by the 5‐HT 2A agonist DOI. This behavior, coupled with past electrophysiological, behavioral and biochemical results, suggests that mGluR2 functions as an autoreceptor in thalamocortical pathways impinging upon the principal output cells, layer V pyramidal cells, of the mPFC.