Srinivasan ThyagaRajan

L-deprenyl, a monoamine oxidase-B inhibitor, has been shown to reverse the age-related decline in sympathetic noradrenergic innervation and immune function in old rats and enhance T cell and NK cell activity in tumor-bearing rats. The objective of the present study was to examine whether deprenyl treatment of old female rats with mammary tumors could augment sympathetic nervous system and immune responses to inhibit the tumor growth. Female Sprague-Dawley rats with spontaneous mammary tumors were administered 0, 2.5 mg, or 5.0 mg/kg body weight (BW)/day deprenyl for i.p. 9 weeks. Tumor diameter, tumor number and body weight were measured throughout the treatment period. At the end of the treatment period, norepinephrine (NE) concentration, interferon-gamma production (IFN-gamma), Con A-induced T lymphocyte proliferation, and percentage of T and B lymphocytes and natural killer cells were measured in the spleen, and the concentrations of monoamines were measured in the medial basal hypothalamus. Relative to saline-treated controls, treatment with deprenyl reduced tumor growth, increased NE concentration, IFN-gamma production and percentage of the CD8+ T lymphocytes in the spleen. In the medial basal hypothalamus, deprenyl treatment increased the concentrations of catecholamines and indoleamine. These results suggest that the anti-tumor effects of deprenyl on spontaneous rat mammary tumors may be achieved via neural-immune signaling in the spleen and medial basal hypothalamus.

The purpose of this study was to investigate the effects of long term treatment with deprenyl, a monoamine oxidase-B inhibitor, on estrous cyclicity, serum PRL, incidence of mammary and pituitary tumors, and monoamine metabolism in the medial basal hypothalamus (MBH) and striatum (ST) of old female rats. Acyclic female Sprague-Dawley rats (15-16 months old) were treated sc with 0, 0.25, or 2.5 mg deprenyl/kg BW.day for more than 8 months. Body weight and food intake were measured every week, and the estrous cycles and development of mammary tumors were monitored throughout the treatment period. At the end of the treatment period, the concentrations of catecholamines, serotonin, and their metabolites in the MBH and ST were determined by HPLC with electrochemical detection. The wet weights of the pituitary, heart, liver, lung, kidney, adrenals, uterus, and ovaries were recorded. Trunk blood was collected for measurement of serum PRL concentrations by RIA. Deprenyl treatment temporarily reestablished estrous cycles in most of the rats. The incidence of pituitary and mammary tumors was markedly reduced in the deprenyl-treated rats compared with that in the saline-treated control rats. Deprenyl had no significant effect on the weights of internal organs. The high dose of deprenyl (2.5 mg/kg) decreased serum PRL concentrations significantly. There were no significant differences in body weight or food intake between the control and deprenyl-treated groups. Deprenyl decreased the concentrations of the monoamine metabolites, dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid, in both the MBH and ST. It had no effect on the concentrations of norepinephrine and dopamine in the MBH, but significantly increased norepinephrine concentrations in the ST and serotonin concentrations in both the MBH and ST (P < 0.05). It is concluded that deprenyl treatment exerted these effects via suppression of monoamine metabolism.