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    Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia

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    Date
    2008-05
    Author
    Gregg, Laura
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    Abstract
    Stress-induced analgesia (SIA) is mediated by mobilization of endocannabinoid lipids such as 2-arachidonoylglycerol (2-AG) in the midbrain periaqueductal gray (PAG). 2-AG may be synthesized on demand to induce SIA through the consecutive activation of two enzymes- phospholipase C (PLC) and diacylglycerol lipase (DGL). We examined whether activation of postsynaptic group I metabotropic glutamate receptors (mGluRs) would enhance SIA because of their known coupling to PLC. Microinjection of the group I mGluR agonist DHPG into the dorsolateral PAG (dPAG) enhanced SIA through a CB1-dependent mechanism. Microinjection of the DGL inhibitors tetrahydrolipstatin (THL) and RHC80267 into the dPAG suppressed SIA. The DHPG-induced enhancement of SIA was blocked by THL. Off-site injections of the active compounds did not alter SIA. Our results support the hypothesis that exposure to environmental stressors stimulates synthesis of 2-AG through the PLC/DGL pathway to induce SIA. Moreover, this process may be initiated by activation of group I mGluRs.
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    http://purl.galileo.usg.edu/uga_etd/gregg_laura_200805_ms
    http://hdl.handle.net/10724/24617
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    • University of Georgia Theses and Dissertations

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