Male and female stress in serotonin transporter knockout mice

Abstract

Serotonin (5-HT) is an important modulator of many physiological, behavioural and developmental processes and it plays an important role in stress coping reactions. Anxiety disorders and depression are stress-related disorders and they are associated with malfunction of the serotonin system, in which the serotonin transporter (5-HTT) plays an important role. 5-Htt knockout (KO) mice represent an artificially hyperserotonergic environment, show an increased anxiety-like behaviour and seem to be a good model to investigate the role of the serotonin system concerning stress reactions and anxiety disorders. As synaptic vesicle proteins (SVPs) seem to be involved in stress reactions we studied the effect of acute immobilization stress on SVP expression in the 5-Htt KO mouse model as well as the expression of the two immediate early genes (IEGs) FBJ osteosarcoma oncogene (c-Fos) and fos-like antigen 2 (Fra-2). Based on gender- and genotype-dependent differences in corticosterone levels we looked for expression differences in the brain by performing a quantitative real time-PCR study using primer pairs specific for the SVPs Synaptotagmin (Syt) I, Syt IV and Syntaxin (Stx) 1a and for the IEGs c-Fos and Fra-2 in five different brain regions in 5-Htt KO and wildtype mice. We found mainly gender-dependent differences but less stress effects on the expression of SVPs. Regarding the expression of IEGs we found stress-, gender- and genotype-dependent differences mainly in hypothalamus.