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ELEVATED tph2 m RNA EXPRESSION IN A RAT MODEL OF CHRONIC ANXIETY
Author(s) -
Donner Nina C.,
Johnson Philip L.,
Fitz Stephanie D.,
Kellen Karen E.,
Shekhar Anantha,
Lowry Christopher A.
Publication year - 2012
Publication title -
depression and anxiety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.634
H-Index - 129
eISSN - 1520-6394
pISSN - 1091-4269
DOI - 10.1002/da.21925
Subject(s) - tph2 , dorsal raphe nucleus , endocrinology , medicine , panic disorder , tryptophan hydroxylase , amygdala , psychology , anxiolytic , raphe nuclei , panic , serotonergic , elevated plus maze , serotonin , anxiety , receptor , psychiatry
Background Allelic variations in TPH 2, the gene encoding tryptophan hydroxylase 2, the rate‐limiting enzyme for brain serotonin (5‐ HT ) biosynthesis, may be genetic predictors of panic disorder and panic responses to panicogenic challenges in healthy volunteers. To test the hypothesis that tph2 m RNA is altered in chronic anxiety states, we measured tph2 expression in an established rat model of panic disorder. Methods We implanted 16 adult, male rats with bilateral guide cannulae and then primed them with daily injections of the corticotropin‐releasing factor ( CRF ) receptor agonist, urocortin 1 ( UCN 1, 6 fmoles/100 nl per side, n = 8) or vehicle (n = 8) into the basolateral amygdaloid complex (BL) for 5 consecutive days. Anxiety‐like behavior was assessed, 24 hr prior to and 48 hr following priming, in the social interaction ( SI ) test. A third group (n = 7) served as undisturbed home cage controls. All rats were killed 3 days after the last intra‐BL injection to analyze tph2 and slc6a4 (gene encoding the serotonin transporter, SERT ) m RNA expression in the dorsal raphe nucleus ( DR ), the main source of serotonergic projections to anxiety‐related brain regions, using in situ hybridization histochemistry . Results UCN 1 priming increased anxiety‐related behavior in the SI test compared to vehicle‐injected controls and elevated tph2, but not slc6a4, m RNA expression in DR subregions, including the ventrolateral DR/ventrolateral periaqueductal gray ( DRVL/VLPAG ), a subregion previously implicated in control of panic‐related physiologic responses. Tph2 m RNA expression in the DRVL/VLPAG was correlated with increased anxiety‐related behavior . Conclusion Our data support the hypothesis that chronic anxiety states are associated with dysregulated tph2 expression .