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Altered locus coeruleus–norepinephrine function following single prolonged stress
dc.contributor.authorGeorge, Sophie A.en_US
dc.contributor.authorKnox, Dayanen_US
dc.contributor.authorCurtis, Andre L.en_US
dc.contributor.authorAldridge, J. Wayneen_US
dc.contributor.authorValentino, Rita J.en_US
dc.contributor.authorLiberzon, Israelen_US
dc.date.accessioned2013-04-08T20:50:07Z
dc.date.available2014-05-01T14:28:28Zen_US
dc.date.issued2013-03en_US
dc.identifier.citationGeorge, Sophie A.; Knox, Dayan; Curtis, Andre L.; Aldridge, J. Wayne; Valentino, Rita J.; Liberzon, Israel (2013). "Altered locus coeruleus–norepinephrine function following single prolonged stress." European Journal of Neuroscience 37(6): 901-909. <http://hdl.handle.net/2027.42/97273>en_US
dc.identifier.issn0953-816Xen_US
dc.identifier.issn1460-9568en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/97273
dc.description.abstractData from preclinical and clinical studies have implicated the norepinephrine system in the development and maintenance of post‐traumatic stress disorder. The primary source of norepinephrine in the forebrain is the locus coeruleus ( LC ); however, LC activity cannot be directly measured in humans, and previous research has often relied upon peripheral measures of norepinephrine to infer changes in central LC –norepinephrine function. To directly assess LC –norepinephrine function, we measured single‐unit activity of LC neurons in a validated rat model of post‐traumatic stress disorder – single prolonged stress ( SPS ). We also examined tyrosine hydroxylase mRNA levels in the LC of SPS and control rats as an index of norepinephrine utilisation. For electrophysiological recordings, 92 LC neurons were identified from 19 rats ( SPS , 12; control, 7), and spontaneous and evoked responses to a noxious event (paw compression) were recorded. Baseline and restraint stress‐evoked tyrosine hydroxylase mRNA expression levels were measured in SPS and control rats ( n  = 16 per group) in a separate experiment. SPS rats showed lower spontaneous activity but higher evoked responses, leading to an enhanced signal‐to‐noise ratio of LC neurons, accompanied by impaired recovery from post‐stimulus inhibition. In concert, tyrosine hydroxylase mRNA expression in the LC of SPS rats tended to be lower at baseline, but was exaggerated following restraint stress. These data demonstrate persistent changes in LC function following stress/trauma in a rat model of post‐traumatic stress, as measured by differences in both the electrophysiological properties of LC neurons and tyrosine hydroxylase mRNA transcription. Single unit activity of LC neurons and TH mRNA levels were measured in the S ingle P rolonged S tress model of P ost‐traumatic stress disorder. SPS decreased rates of spontaneous discharge, exaggerated phasic responses of LC neurons and augmented stress‐enhanced TH mRNA expression. These data demonstrate sustained LC ‐ NE system abnormalities in SPS , providing an opportunity to study the interaction between LC ‐ NE system, and other PTSD ‐like physiological and behavioral changes seen in this model.en_US
dc.publisherAmerican Psychiatric Pressen_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherAnimal Modelsen_US
dc.subject.otherPost‐Traumatic Stressen_US
dc.subject.otherNoradrenergicen_US
dc.subject.otherTyrosine Hydroxylaseen_US
dc.subject.otherRaten_US
dc.titleAltered locus coeruleus–norepinephrine function following single prolonged stressen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.identifier.pmid23279008en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/97273/1/ejn12095.pdf
dc.identifier.doi10.1111/ejn.12095en_US
dc.identifier.sourceEuropean Journal of Neuroscienceen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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