Show simple item record

dc.contributor.authorGregg, Laura Corrine
dc.date.accessioned2014-03-04T18:27:54Z
dc.date.available2014-03-04T18:27:54Z
dc.date.issued2010-05
dc.identifier.othergregg_laura_c_201005_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/gregg_laura_c_201005_phd
dc.identifier.urihttp://hdl.handle.net/10724/26333
dc.description.abstractThe endocannabinoid 2-arachidonoylglycerol (2-AG) produces adaptive changes in pain responses following exposure to environmental stressors. This phenomenon, termed stress-induced analgesia (SIA), is dependent upon mobilization and accumulation of 2-AG in the periaqueductal gray (PAG). 2-AG within the PAG may activate CB1 receptors on GABAergic neurons to reduce inhibition of output neurons that form part of a descending antinociceptive pathway. Alternatively, 2-AG may activate CB1 receptors on glutamatergic neurons to inhibit pro-nociceptive pathways that facilitate pain. 2-AG acts as a retrograde signal that binds to CB1 receptors to produce antinociception. However, the mechanisms contributing to the mobilization of 2-AG are only beginning to be discovered. We examined the role of presynaptic group III metabotropic glutamate receptors (mGluRs), which are negatively coupled to adenylyl cyclase and reduce GABAergic inhibition, on the phenomenon of SIA in the PAG. Microinjection into the dorsolateral PAG (dlPAG) of the group III mGluR agonst L-AP4 produced a dose-dependent enhancement of SIA through a CB1-dependent mechanism. By contrast, off-site injections of L-AP4 failed to enhance SIA. The L-AP4-induced enhancement of SIA was blocked by the group III mGluR antagonist UBP1112 at a dose that was found to be ineffective in modulating SIA when administered alone. Microinjection of the group III mGluR antagonist UBP1112 into the dlPAG produced a dose-dependent suppression of SIA and also blocked the enhancement of SIA induced by L-AP4. This effect involved the dorsolateral PAG because off-site injections failed to alter SIA. Our findings suggest a previously unrecognized role for group III mGluRs in controlling endocannabinoid-dependent stress-induced analgesia, presumably by controlling the mobilization of endocannabinoids, likely 2-AG, in the PAG.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectendocannabinoid
dc.subjectantinociception
dc.subjectmetabotropic glutamate receptor
dc.titleActivation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentBiomedical and Health Sciences Institute
dc.description.majorNeuroscience
dc.description.advisorAndrea Hohmann
dc.description.committeeAndrea Hohmann
dc.description.committeePhilip Holmes
dc.description.committeeJonathon Crystal


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record