Long-Term Reduction in Anxiety Levels During the Promotion Phase of Mammary Adenocarcinoma Induced by Dimethylbenz (a) Anthracene in Female Sprague-Dawley Rats

Background/Aims: It has been reported that long-term neuroendocrine dysregulation of the Hypothalamic- Pituitary-Gonadal (HPG) axis and of the Hypothalamic-Pituitary-Adrenal (HPA) axis precede the appearance of mam- mary adenocarcinoma induced by 7, 12-Dimethylbenz(a)anthracene (DMBA) in female rats. In the present study, we in- vestigated the hypothesis that DMBA may also induce long-term changes in anxiety levels. Methods: Female Sprague-Dawley rats were given a single dose of DMBA( 75 mg/kg) in 1ml sesame oil, or 1ml of ses- ame oil(control rats), at 55 days of age. Then,DMBA-treated and control rats were observed, monitoring their oestrous cy- cle. One month after administering the DMBA, anxiety levels were measured in an open-field test.The test device was an arena with a floor of 100 cm x 100 cm and a wall of 40 cm high, with white floor and walls.The floor was divided into 25 equal squares ( 16 peripheral and 9 central squares ). The statistical analysis was a two-factor analysis of variance. Results: Overall statistical scores showed that DMBA-treated animals had: a) greater ambulatory activity and more rearing behaviour in the central squares, but not in the peripheral squares, and b) deposited fewer faecal boli. Conclusions: Greater exploration of the less protected squares (in the centre), lower frequency of defecation and a greater number of rearings show a lower level of anxiety. Changes in HPG axis activity and a decrease in HPA axis activity, as previously reported, may explain the reduction in anxiety levels after treatment with the mammary carcinogen.