NA inputs to the BNST are implicated in stress and anxiety. The alpha-2 adrenoceptor antagonist YO increases transmitter release from NA terminals, activates the HPA axis, and is anxiogenic. We have shown that YO dose-dependently activates Fos in the BNST and PVN. We also have shown that YO inhibits food intake and supports conditioned flavor avoidance. Recruitment of NA inputs to the BNST may underlie these neural and behavioral effects of YO. In the present study, NA inputs to the ventrolateral BNST were lesioned bilaterally by microinjecting saporin toxin conjugated to DBH antibody (DSAP). Ten to 14 days after surgery, DSAP (n=9) and sham rats (n=7) were food-deprived for 24 hrs. Half of the rats in each group were injected i.p. with saline vehicle, and half were injected with YO (5.0 mg/kg). Food was returned 30 min later, and cumulative intake was recorded. The experiment was later repeated in a counterbalanced design. YO significantly inhibited food intake to a similar extent in sham and DSAP rats. The second experiment examined the ability of YO to support conditioned flavor avoidance. In a two-bottle choice test, water-deprived rats significantly avoided drinking water containing flavors previously paired with YO treatment. The magnitude of conditioned aversion was similar in DSAP and sham rats. The third experiment examined YO-induced anxiety-like behaviors on the elevated plus maze. DSAP and sham rats were acclimated to handling, transport and timecourse of the experiment for 3 days prior to the first test day. Rats were left undisturbed in a room adjacent to the testing room for 30 minutes. Then, each rat was injected i.p. with either YO or saline. Thirty minutes after injection rats were placed on the elevated plus maze for 5 minutes while being recorded. YO-induced increases in anxiety-like behavior were attenuated in DSAP rats. Finally, DSAP and sham rats were injected with YO or vehicle and perfused with fixative 90120 minutes later. Brain sections were processed to reveal lesion extent and Fos activation patterns. YO activated significantly fewer BNST neurons and CRH-positive PVN neurons in DSAP rats compared to sham controls. DBH immunolabeling in the BNST and medial parvocellular PVN was depleted in DSAP rats, whereas the lateral magnocellular PVN was unaffected. The NST and VLM contained significantly fewer NA neurons in DSAP rats compared to sham controls; however, YO activated similar proportions of the NA neurons that remained. We conclude that NA neurons innervating the BNST collateralize to innervate the medial parvocellular PVN, and that these NA inputs are necessary for YO to activate Fos within the BNST and PVN. Additionally, these inputs contribute to the YO-induced anxiety-like behaviors on the elevated plus maze. However, the NA inputs to the BNST are unnecessary for YO to inhibit food intake or support conditioned flavor avoidance, suggesting that other neural pathways are sufficient for these responses.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08052005-124958 |
| Date | 06 July 2006 |
| Creators | Banihashemi, Layla |
| Contributors | Anthony A. Grace, John P. Card, Linda M. Rinaman |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-08052005-124958/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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