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5-Ht1a Antagonism within the Bed Nucleus of the Stria Terminalis Modulates Anxiety-Like Behaviors in Rats

Substantial evidence suggests that serotonin (5-HT) activation within the brain modulates anxiety-like behavior. The bed nucleus of the stria terminalis (BNST) has been argued to mediate anxiety-like behavioral responding, and the activation of 5-HT systems may modulate anxiety-like behavior via the release of 5-HT within the BNST. Prior studies have suggested that the 5-HT1, 7 agonist 5-carboxyamidotrytamine (5-CT) is anxiolytic, which is consistent with a reduction in BNST activity via the activation of postsynaptic 5- HT1A receptors. However the anxiolytic effects of 5-CT could also have been mediated by 5-HT7 receptor activation. Hence, to isolate the effects of 5-HT1A on anxiety-like behavior, we infused the 5-HT1A antagonist WAY-100635 (0, 0.04, 0.4, and 4.0 μg/μl in saline vehicle) into the BNST of rats immediately before social interaction or acoustic startle testing. For social interaction testing pairs of rats were administered two 5-sec 1- mA footshocks immediately after infusion, removed from the chamber and measured for social interaction in a separate testing apparatus. For acoustic startle testing, rats were placed in boxes and measured for the percentage increase in test (post-infusion) startle from baseline (pre-infusion) startle. Anxiety levels were operationalized as the amount of social interaction per line cross and the percentage increase in startle following drug infusion. WAY-100635 dose dependently decreased social interaction, indicative of an anxiogenic effect. Interestingly, 0.4μg/μl of WAY-100635 decreased startle, indicative of an anxiolytic effect. These data suggest that activation of the 5-HT systems modulates anxiety-like behavior by altering activity within the BNST.

Identiferoai:union.ndltd.org:uvm.edu/oai:scholarworks.uvm.edu:graddis-1191
Date06 October 2008
CreatorsRhodes, Kimberly
PublisherScholarWorks @ UVM
Source SetsUniversity of Vermont
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceGraduate College Dissertations and Theses

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