Abstract
The aim of this study was to investigate the effects of a mixed dietary intervention on behavioral symptoms in serotonin transporter knockout (5-HTT/) rats modeling the human 5-HTT length polymorphic region short-allele. Twenty female 5-HTT/ and 19 wild-type (5-HTT/) rats were fed for 3 months on a mixed polyunsaturated fatty acid (PUFA) diet comprising n-3 PUFAs, B vitamins and phospholipids, or an isocaloric control diet, and a subgroup was subsequently tested in an array of anxiety-related behavioral tests. All brains were harvested and immunostained for doublecortin, a neurogenesis marker. In addition, hippocampal volume was measured. 5-HTT/ rats on the control diet displayed increased anxiety-related behavioral responses, and impaired fear extinction. These effects were completely offset by the mixed PUFA diet, whereas this diet had no behavioral effect in 5-HTT/ rats. In parallel, dentate gyrus doublecortin immunoreactivity was increased in 5-HTT/ rats fed on the control diet, which was reversed by the mixed PUFA diet. Hippocampal volume was unaffected by the mixed PUFA diet in 5-HTT/ subjects, whereas it increased in 5-HTT/ rats. We conclude that a mixed n-3 PUFA diet ameliorates anxiety-related symptoms in a genotype-dependent manner, potentially by normalizing neurogenesis. We suggest that such a mixed diet may serve as an attractive adjuvant to treat anxiety in 5-HTT length polymorphic region short-allele carriers.
