Prenatal maternal stress alters depression-related symptoms in a strain - and sex-dependent manner in rodent offspring.

Stress during pregnancy adversely affects foetal development and leads to later behavioural outcomes in offspring. Preclinical studies have reported conflicting effects of prenatal stress on depression-related symptoms in rodent offspring. This study aimed to study the combined effect of strain and sex on prenatal stress outcomes in a single study. To this end, male and female offspring from outbred Wistar and inbred Lewis rats, and outbred NMRI and inbred C57BL6 mice were compared. As outcomes we focussed on depression-related behaviour and related molecular and neurochemical parameters. Prenatally stressed and non-stressed offspring were subjected to the sucrose preference, novelty-suppressed feeding, tail suspension, and forced swim tests. We measured basal and stress-induced corticosterone levels in the serum, and brain-derived-neurotrophic-factor (BDNF), interleukin-1ß, tumor necrosis factor-α, glutamate and serotonin in the brain to determine changes in hypothalamic-pituitary-adrenal-(HPA)-axis function, neuroplasticity, neuroinflammation, and neurotransmission. Our findings revealed that prenatal stress increases depression-like behaviour, HPA-axis (re) activity, pro-inflammatory cytokines and glutamate levels, and decreases BDNF and serotonin levels in a strain and sex-dependent manner in rodent offspring. Overall, male and female Lewis rats, female Wistar rats, male NMRI mice and female C57BL6 mice were found to be most responsive to prenatal stress. Based on these results, we conclude that genetic background and sex contribute to the great diversity in the effects of prenatal maternal stress in rodents.

Deletion of the serotonin transporter perturbs BDNF signaling in the central amygdala following long-access cocaine self-administration.

BACKGROUND: Human neuroimaging studies indicate that the amygdala plays a key role in cocaine addiction. One key plasticity factor that modulates effects of cocaine on the brain is Brain-Derived Neurotrophic Factor (BDNF). A wealth of evidence shows that cocaine exposure alters BDNF signaling in corticolimbic structures, but, surprisingly, such evidence is very limited for the amygdala. Additionally, while BDNF is strongly regulated by serotonin levels and inherited serotonin transporter down-regulation is associated with increased vulnerability to cocaine addiction, the effects of serotonin transporter genotype on BDNF signaling in the amygdala under naïve and cocaine exposure conditions are unknown. METHODS: We measured BDNF signaling in the central amygdala of wild-type and serotonin transporter knockout rats 24 h into withdrawal from long-access cocaine self-administration. RESULTS: In wild-type rats mature BDNF (mBDNF) protein levels were decreased, whereas the phosphorylation of its receptor TrkB as well as of its intracellular signaling molecules Akt and ERK1 were increased. mBDNF protein expression and its signaling in cocaine-naïve serotonin transporter knockout rats resembled that of wild-type rats with a history of long-access cocaine self-administration. Interestingly, cocaine-exposed serotonin transporter knockout rats showed increased BDNF levels, with no signs of phospho-TrkB receptor coupling to phospho-Akt and phospho-ERK1. CONCLUSIONS: Long-access cocaine self-administration dysregulates BDNF signaling in the central amygdala. Vulnerability to cocaine addiction is associated with dysregulation of this signaling.