Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as
genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated
brain-derived neurotrophic factor (
BDNF) in MDD pathology, as a genetic risk factor and
a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating
BDNF, which is present in rats and humans. Therefore, heterozygous
BDNF (
BDNF+/- ) rats were tested for affective behaviours and accompanying expression of key genes associated with
affective disorders in the brain. We found that
BDNF+/- rats, which have reduced
BDNF levels in brain and plasma, displayed symptoms of
anhedonia, a core symptom of MDD, and anxiety-like behaviour, but no behavioural despair or
cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and
affective disorders. Hence,
glucocorticoid receptor,
neuregulin 1 and disrupted-in-
schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN+/- rats, whereas
FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in
BDNF levels alters expression of genes associated with
affective disorders, which may contribute to the development of depressive-like symptoms.