Effects of nefazodone on the development of experimentally induced tumors in stressed rodents.
BACKGROUND
Anxiety and depression are commonly encountered in patients with cancer and constitute risk and prognostic factors for the disease. Although previous findings do not support an overall association between the use of antidepressants and higher prevalence of cancer, results for serotonin uptake inhibitors are not entirely reassuring.


OBJECTIVE
We evaluated the effects of nefazodone, a serotonin and norepinephrine (NE) reuptake inhibitor and 5-HT(2A) receptor antagonist antidepressant, on the appearance of breast cancer induced by mammary tumor virus (MTV) in mice, and on the development of lung metastases in rats injected intravenously with Walker 256 (W-256) carcinosarcoma cells.


METHODS
Female C3H/He mice carrying the MTV were monitored for mammary tumor incidence and latent periods while being treated with a daily intraperitoneal injection with placebo or nefazodone. Rats were administered 10(4) W-256 cells, exposed to a chronic auditory stressor for 8 days, and then killed to evaluate metastatic nodules in the lungs.


RESULTS
Although all of the mice were potential candidates for MTV-induced breast cancer, those treated with nefazodone were partially protected against adverse effects of stress induced by the daily administration of placebo on both parameters. Relative to placebo, nefazodone reduced the stress-induced increase in the number and percentage area of metastases in the frontal section through pulmonary hilus and increased the survival periods of rats given W-256 cells and exposed to a chronic auditory stressor.


CONCLUSIONS
Our results provide evidence of the beneficial effects of nefazodone against the adverse effects of stress on tumor development and metastaticity in rodents, but did not show significant effects in unstressed rodents.
Freire-Garabal
Manuel
M
Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine, C/San Francisco, s/n. Santiago de Compostela, A Coruna, 15782, Spain. fffregar@usc.es
Rey-Méndez
Manuel
M
García-Vallejo
Luis A
LA
Balboa
José
J
Suárez
José M
JM
Rodrigo
Elena
E
Brenlla
Julio
J
Núñez
María J
MJ
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002279:Carcinoma 256, Walker / Q000473:pathology; D008297:Male; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000517:prevention & control*; D010879:Piperazines; D051381:Rats; D017207:Rats, Sprague-Dawley; D012192:Retroviridae Infections / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology*; D014230:Triazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000473:pathology
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone