Elsevier

Biological Psychiatry

Volume 67, Issue 4, 15 February 2010, Pages 339-345
Biological Psychiatry

Archival Report
5-Hydroxytryptamine 2C Receptors in the Basolateral Amygdala Are Involved in the Expression of Anxiety After Uncontrollable Traumatic Stress

https://doi.org/10.1016/j.biopsych.2009.09.011Get rights and content

Background

Exposure to uncontrollable stressors often increases anxiety-like behavior in both humans and rodents. In rat, this effect depends on stress-induced activity within the dorsal raphe nucleus (DRN). However, the role of serotonin in DRN projection regions is largely unknown. The goals of this study were to 1) assess the effect of uncontrollable stress on extracellular serotonin in the basolateral amygdala during the anxiety test, 2) determine whether DRN activity during a poststress anxiety test is involved in anxiety-like behavior, and 3) determine the role of the serotonin 2C receptor (5-HT2C) in uncontrollable stress-induced anxiety.

Method

Rats were exposed to tail shocks that were either controllable or uncontrollable. On the following day, anxiety-like behavior was assessed in a Juvenile Social Exploration (JSE) test. Basolateral amygdala (BLA) extracellular serotonin concentrations were assessed during JSE by in vivo microdialysis 24 hours after uncontrollable stress, controllable stress, or no stress. In separate experiments, drugs were administered before the JSE test to inhibit the DRN or to block 5-HT2C receptors.

Results

Exposure to uncontrollable shock reduced later social exploration. Prior uncontrollable stress potentiated serotonin efflux in the BLA during social exploration, but controllable stress did not. Intra-DRN 8-OH-DPAT and systemic and intra-BLA 5-HT2C receptor antagonist SB 242,084 prevented the expression of potentiated anxiety in uncontrollably stressed rats. Intra-BLA injection of the 5-HT2C agonist CP 809,101 mimicked the effect of stress.

Conclusions

These results suggest that the anxiety-like behavior observed after uncontrollable stress is mediated by exaggerated 5-HT acting at BLA 5-HT2C receptors.

Section snippets

Rats

Adult (60–70 days old and weighing 275–350 g at the time of testing) and juvenile (28–32 days old and weighing 90–100 g at the time of testing) male Sprague-Dawley (Harlan, Indianapolis, Indiana) rats were used in all experiments. Rats were housed with free access to food and water in groups of two for microinjection experiments, in groups of four when drugs were administered intraperitoneally (IP), and in single cages for the microdialysis experiment. The vivarium maintained a 12-hour

Extracellular BLA 5-HT During and Following Social Exploration

Importantly, all rats in the ES group learned to escape the tail shock, quickly reached the maximum response criterion, and maintained escape behavior as previously reported (14). Only rats with dialysis probes at least 50% within the BLA were included (Figure 1); the resulting groups had NS = 6–7. Prior stress did not alter basal 5-HT, means (SEM): ES = .272 (.03), IS = .267 (.05), HC = .274 (.04) pg/20 μL. Extracellular 5-HT was converted to percentage of baseline by dividing each sample by

Discussion

Here we explored the role of the DRN, 5-HT, and BLA 5-HT2C receptors in uncontrollable stress-induced anxiety-like behavior in the JSE test. Consistent with our prior work and that of others, exposure to an uncontrollable stressor (IS) reduced the rat's tendency to investigate a juvenile conspecific (12, 13, 37), whereas equal controllable stress did not (12, 36). The hypothesis has been that IS produces an intense activation of DRN 5-HT neurons, leading to sensitization of these neurons via

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