Abstract
We previously showed that chronic i.c.v. antagonism of metabotropic glutamate receptors (mGluRs) concurrently with s.c. morphine significantly attenuated precipitated withdrawal symptoms. Conversely, acute i.c.v. injection of a selective group II mGluR antagonist just before the precipitation of withdrawal exacerbated abstinence symptoms.
In the present study, we showed that acute i.c.v. administration of the non-selective mGluR agonist 1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD), as well as the group II selective agonist (2S,1′R,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV), significantly attenuated the severity of precipitated withdrawal symptoms.
From these results we hypothesize that chronic opioid treatment may indirectly induce a desensitization of group II mGluRs, which contributes to the development of dependence.
Keywords: Morphine; dependence; (1S,3R)-ACPD; (1S,3S)-ACPD; DHPG; DCG-IV; L-AP4; metabotropic glutamate receptor; precipitated withdrawal
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