Social isolation and predator scent tests alter brain BDNF levels differentially according to gender, in rats and effects of fluoxetine

Abstract

We compared different stress conditions on brain BDNF levels, in rats exposed to social isolation test (SIT) and predator scent tests (PST). BDNF expression in the frontal cortex, hippocampus, and amygdala was compared, and effects of chronic fluoxetine (FLU) treatment were evaluated. Rats were exposed to SIT and PST for one month. FLU was given (5 mg/kg/day, ip) throughout stress procedures. Controls, stress, and treatment groups were evaluated in elevated plus maze, anxiety scores were calculated. BDNF expression was determined by Western blot. SIT and PST induced anxiety in both sexes, females had greater anxiety scores than males (p<0.05). FLU restored anxiety scores in both sexes (p<0.01) in both tests. Male and female rats exhibited reduced cortical BDNF levels in SIT (p<0.001). PST reduced cortical BDNF in females, but increased in males. Hippocampal BDNF expression was lowered in SIT (p<0.01) and PST (p<0.001) in both sexes. Female rats had 40% lower BDNF expression than males in the amygdala in SIT. FLU did not restore cortical BDNF in females in both tests, but reduced increased BDNF levels in males in PST (p<0.001). FLU did not restore reduced brain BDNF in males in the hippocampus and amygdala, but restored in hippocampus, in females. Our findings indicate that sex differences must be considered in studies related to mood disorders of animal models, and suggest that BDNF expression in different brain regions are altered differentially in a gender-dependent manner in rats. Antianxiety effect of FLU is not mediated through increasing BDNF activity in cortex in both genders. Increased BDNF in hippocampus and amygdala may reflect antidepressant effect of FLU in female rats, but not in males.

Effect of combination fluoxetine and exercise on prefrontal BDNF, anxiety-like behavior and fear extinction in a female rat model of post-traumatic stress disorder (PTSD): a comparison with male animals

“…It has been shown that both the antidepressant drug fluoxetine and exercise are able to increase BDNF expression in the brain exposed to stress [ 26 , 28 , 36 ], and our results are consistent with these findings. In this regard, exercise induces BDNF enhancement during extinction consolidation and, consequently, reduces threat expectancies following reinstatement in PTSD [ 37 ].…”

“…The findings were similar to that in male PTSD animals in our previous study [ 26 ]. BDNF changes after stress have been frequently reported in several studies [ 28 – 31 ] and our study confirms these findings. Since BDNF has been shown to have an essential role in mediating stress-related pathophysiological changes in the brain [ 32 ] these findings are expectable.…”

“…In Aykaç and colleagues' study, no significant difference was found between males and females in cortical BDNF levels after the social isolation test, however, female rats had lower amygdala BDNF than males after the test [ 28 ]. Based on the mentioned study, it is probable that the difference in findings between males and females originated from the region of the brain collected for BDNF measurement.…”

“…Based on the mentioned study, it is probable that the difference in findings between males and females originated from the region of the brain collected for BDNF measurement. In other words, stress-induced BDNF alteration in the distinct brain parts differs in a sex-dependent manner [ 28 ]. Since the prefrontal region has been shown to be one of the involved parts in PTSD, the present study assessed prefrontal BDNF and similar results were found in males and females.…”

“…It is worth mentioning that although some sex differences in the effect of interventions on stress-exposed subjects [ 6 , 28 ] have been reported, the accurate conclusion needs to compare intervention-induced changes with the normal scores in males and females separately. It is probable that the baseline score is different in a sex-specific manner and consequently leads to different final results between males and females.…”