5-HT1B mRNA regulation in two animal models of altered stress reactivity

Background: Acute stress has profound effects on serotonergic activity, but it is not known whether alterations in the serotonin system can predispose individuals to exaggerated stress responses. We examined the regulation of 5-HT1B and 5-HT1A mRNA in two rodent models of differential sensitivity to stress; congenital learned helplessness (cLH) and handling and maternal separation (HMS). Methods: 5-HT1B and 5-HT1A mRNAs in brain tissue sections were quantitated by in situ hybridization from control, stress-sensitive, and stress-resistant male rats in the HMS model and stress-sensitive and stress-resistant rats (both males and females) in the cLH model. Dorsal raphe nucleus, striatum, and hippocampus were examined. Results: The main result was that dorsal raphe 5-HT1B mRNA was substantially elevated (63-73%) in male rats in the stress-resistant group of both models compared with stress-sensitive animals, 5-HT1B mRNA in female rats did not differ between groups in the cLH model. There were no differences in 5-HT1A mRNA between HMS groups. Conclusions: These findings suggest that 5-HT1B autoreceptor regulation is altered in animals with diminished stress reactivity. These results suggest that 5-HT1B autoreceptors in unstressed and acutely stressed animals differ, indicating the importance of state versus trait changes in serotonin function in animal models of anxiety and depression.