| Abstract No.: | C-E3163 |
| Country: | Canada |
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| Title: | COMPARING THE EFFECTS OF THE SELECTIVE ESTROGEN RECEPTOR MODULATORS TAMOXIFEN AND RALOXIFENE ON SUCROSE DRINKING AND GUSTATORY CONDITIONING (CTA) IN FEMALE RATS. |
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| Authors/Affiliations: | 1 Melissa Fudge*; 1 Martin Kavaliers; 1 Klaus-Peter Ossenkopp;
1 The University of Western Ontario, London, ON, Canada
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| Content: | Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs) that are currently used or proposed for use in the prevention and treatment of breast cancer. They have the dual effect of working as both an estrogen receptor agonist and antagonist depending on the target tissue. However, they do not share the same agonist/antagonist profiles and have been reported to produce differential effects depending on the target tissue. It is, therefore, possible that tamoxifen and raloxifene may differentially modulate the conditioned effects on intake produced by estrogen. Objectives: The purpose of the present study was to investigate and compare whether tamoxifen and raloxifene produce conditioned taste avoidance (CTA) in female rats, which has previously been shown with estradiol treatment. Materials and Methods: Ovariectomized-female Long Evans rats were treated with either tamoxifen (1 and 10 mg/kg, ip), 17β-estradiol (E2, 50 μg/kg, sc), or raloxifene (3 mg/kg, sc) and appropriate vehicles. As well, an uninjected control group was also examined. The experimental procedure consisted of three conditioning days and one test day, each separated by 5 days. On these experimental days, all animals were injected 20 minutes prior to access to 0.3M sucrose for 30 minutes in the lickometer apparatus to measure drinking behaviors. This was then followed by 30 minutes in an automated open field to record both horizontal and vertical activity, as well as thigmotaxis (a measure of anxiety). Results: On Conditioning Days 2 and 3, E2 and tamoxifen (1 and 10 mg/kg) significantly reduced sucrose drinking compared to vehicle and uninjected controls. The reduction in drinking produced by tamoxifen (1 and 10 mg/kg) was significantly more robust than E2. Raloxifene also significantly reduced sucrose drinking on Conditioning Days 2 and 3 compared to controls. On the Test Day, CTA was observed in 17β-estradiol, tamoxifen (1 and 10 mg/kg) and raloxifene compared to their appropriate vehicle and uninjected controls. No significant effects on locomotor activity or thigmotaxis were observed. Conclusion: These results show that both tamoxifen and raloxifene produce CTA. When comparing the effects of tamoxifen and E2, CTA formation was more rapid with tamoxifen then E2. |
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