Beta-Adrenergic Blockade Decreases the Neuroimmune Changes in Mice Induced by Cohabitation with an Ehrlich Tumor-Bearing Cage Mate

Neuroimmunomodulation. 2017;24(1):40-53. doi: 10.1159/000477938. Epub 2017 Aug 9.

Abstract

Objectives: Cohabitation with Ehrlich tumor-bearing (ETB) mice induced behavioral, neurochemical, hormonal, and immune effects in the conspecifics as a consequence of stress-induced activation of the sympathetic nervous system (SNS) with catecholamine release. In the current study, the nonspecific β-AR blocker d,l-propranolol and the specific β2-AR blocker ICI-118.551 were employed as pharmacological tools to assess the extent to which catecholamines participated in the effects induced by cohabitation with ETB mice.

Methods: Two experiments were performed, 1 with d,l-propranolol treatment and the other with ICI-118.551. One mouse in the experimental group was called the "companion of the sick partner" (CSP) since it was forced to live in the same cage with 2 (experiment 1) or 1 (experiment 2) cage mate that had been i.p. injected with 5 × 106 Ehrlich tumor cells.

Results: The d,l-propranolol treatment, but not the ICI-118.551 treatment, attenuated the effects of cohabitation with 2 ETB mice on both open-field behavior and the hypothalamic levels and turnover rate of norepinephrine. The 2 β-AR blockers were unable to change the serum corticosterone levels and adrenal weights of the CSP mice; however, these drugs abrogated the effects of cohabitation on neutrophil oxidative burst and phagocytosis. Finally, an increase in the 5-HT turnover rate was observed in the olfactory bulb of CSP mice compared to their respective controls, an effect that was not modified by β-AR blockade.

Conclusion: These results confirm and strengthen our hypothesis that the SNS is involved in the effects induced by cohabitation with ETB mice and point towards β2-AR participation in the immune effects analyzed.

Keywords: Behavior; Catecholamines; Cohabitation with a sick conspecific; ICI-118.581; Neutrophils; Serotonin; Stress; d,l-Propranolol.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenergic Agents / pharmacology*
  • Animals
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Carcinoma, Ehrlich Tumor / immunology*
  • Carcinoma, Ehrlich Tumor / metabolism
  • Carcinoma, Ehrlich Tumor / psychology*
  • Catecholamines / metabolism
  • Corticosterone / blood
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Female
  • Flow Cytometry
  • Illness Behavior / drug effects
  • Interpersonal Relations*
  • Mice

Substances

  • Adrenergic Agents
  • Catecholamines
  • Corticosterone