The soya isoflavone content of rat diet can increase anxiety and stress hormone release in the male rat
- 193 Downloads
Most commercial rodent diets are formulated with soya protein and therefore contain soya isoflavones. Isoflavones form one of the main classes of phytoestrogens and have been found to exert both oestrogenic and anti-oestrogenic effects on the central nervous system. The effects have not been limited to reproductive behaviour, but include effects on learning and anxiety and actions on the hypothalamo-pituitary axis. It is therefore possible that the soya content of diet could have significant effects on brain and behaviour and be an important source of between-laboratory variability.
To determine whether behaviour in two animal tests of anxiety, and stress hormone production, would differ between rats that were fed a diet which was free of soya isoflavones and other phytoestrogens (iso-free) and those that were fed a diet which contained 150 μg/g of the isoflavones genistein and daidzein (iso-150). This controlled diet has an isoflavone concentration similar to that in the maintenance diet routinely used in our institution.
Male rats were randomly allocated to the iso-free and iso-150 diets and their body weights and food and water consumption were recorded for 14 days. They were then maintained on the same diets, but housed singly for 4 days, before testing in the social interaction and elevated plus-maze tests of anxiety. Corticosterone concentrations in both dietary groups were determined under basal conditions and after the stress of the two tests of anxiety. Vasopressin and oxytocin concentrations were determined after brief handling stress.
The groups did not differ in food or water intake, body weight or oxytocin concentrations. Compared with the rats fed the iso-free diet, the rats fed the iso-150 diet spent significantly less time in active social interaction and made a significantly lower percentage of entries onto the open arms of the plus-maze, indicating anxiogenic effects in both animal tests. The groups did not differ in their basal corticosterone concentrations, but the iso-150 group had significantly elevated stress-induced corticosterone concentrations. Stress-induced plasma vasopressin concentrations were also significantly elevated in the iso-150 diet group compared with the iso-free rats.
Major changes in behavioural measures of anxiety and in stress hormones can result from the soya isoflavone content of rat diet. These changes are as striking as those seen following drug administration and could form an important source of variation between laboratories.
KeywordsPhytoestrogen Anxiety Social interaction Elevated plus-maze Corticosterone Vasopressin Oxytocin
These experiments were supported by a grant from the Dunhill Medical Trust. We are indebted to Dr. Tobin of Harlan Teklad UK Ltd. for the detailed calculations of the isoflavone content of our diet.
- Baldwin HA, File SE (1989) Flumazenil prevents the development of chlordiazepoxide withdrawal in rats tested in the social interaction test of anxiety. Psychopharmacology 97:424–426Google Scholar
- Boettger-Tong H, Murthy L, Chiappetta C, Kirkland JL, Goodwin B, Adlercreutz H, Stancel GM, Makela S (1998) A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens. Environ Health Perspect 106:369–373Google Scholar
- File SE (1994) Chronic exposure to noise modifies the anxiogenic response, but not the hypoactivity, detected on withdrawal from chronic ethanol treatment. Psychopharmacology 116:369–372Google Scholar
- File SE, Andrews N (1991) Low but not high doses of buspirone reduce the anxiogenic effects of diazepam withdrawal. Psychopharmacology 105:578–582Google Scholar
- File SE, Hyde JR (1978) Can social interaction be used to measure anxiety? Br J Pharmacol 62:19–24Google Scholar
- File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53Google Scholar
- File SE, Vellucci SV (1978) Studies on the role of ACTH and of 5-HT in anxiety, using an animal model. J Pharm Pharmacol 30:105–110Google Scholar
- File SE, Baldwin HA, Hitchcott PK (1989) Flumazenil but not nitrendipine reverses the increased anxiety during ethanol withdrawal in the rat. Psychopharmacology 98:262–264Google Scholar
- File SE, Kenny PJ, Ouagazzal AM (1998) Bimodal modulation by nicotine of anxiety in the social interaction test: role of the dorsal hippocampus. Behav Neurosci 112:1423–1429Google Scholar
- Husain K, Manger WM, Rock TW, Weiss RJ, Weiss RA, Birkner J, Dufton S, Hart C, Frantz AG (1975) Plasma vasopressin (VP) in rats: effect of stressful stimuli. Clin Res 13:573AGoogle Scholar
- Kampov-Polevoy AB, Matthews DB, Gause L, Morrow AL, Overstreet DH (2000) P rats develop physical dependence on alcohol via voluntary drinking: changes in seizure thresholds, anxiety, and patterns of alcohol drinking. Alcohol Clin Exp Res 24:278–284Google Scholar
- Kao YC, Zhou C, Sherman M, Laughton CA, Chen S (1998) Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: a site-directed mutagenesis study. Environ Health Perspect 106:85–92Google Scholar
- Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529Google Scholar