Behavioral characterization of A/J and C57BL/6J mice using a multidimensional test: Association between blood plasma and brain magnesium-ion concentration with anxiety

Up to 29% of all adults will experience an anxiety-related disorder during their lives. Treatment of these disorders is still difficult and the exact mechanisms and pathways behind anxiety disorders remain to be elucidated. Although evidence exists for genetically based susceptibility of human psychiatric diseases, risk genes have rarely been identified up to now. Inbred mouse strains are, together with the crosses and genetic reference populations derived from them, important tools for the genetic dissection of complex behavioral traits in the mouse. Thus, inbred mouse models of human anxiety may be a potent starting tool to search for candidate genes in mice, which could then via comparative genomics be translated to the human situation. In this paper we investigate whether the A/J and C57BL/6J mouse inbred strains differ in a limited number of motivational systems (anxiety, exploration, memory, locomotion, and social affinity), but especially in anxiety-related behavior from each other. Young adult individuals from both genders of A/J and C57BL/6J strains were behaviorally phenotyped using a multidimensional test: the modified hole board. This paradigm basically is a combination of the traditional hole board and the open field test allowing to test for anxiety-related avoidance behavior, risk assessment, arousal, exploration, memory, locomotor activity, and social affinity, using just one single test. An acute, aversive stimulus (intra-peritoneal injection with saline) was applied to the animals to test for the robustness of their behavioral phenotype. In addition, presumed physiological indicators for anxiety (circulating glucose, cholesterol, and corticosterone, adrenal tyrosine hydroxylase, and blood plasma and brain magnesium) were investigated. It could be concluded that C57BL/6J and A/J mice differ with respect to almost all tested motivational systems. For some measures, including anxiety-related behavioral parameters, there were clear gender effects. The high-anxiety phenotype of A/J mice could be shown to represent a primary and robust characteristic. Further, blood plasma and brain magnesium levels were significantly correlated with several anxiety-related behavioral parameters. These results emphasize the hypothesized, and possibly causal, association between magnesium status and emotionality.

Research Highlights►A/J and C57BL/6J mice behaviorally differed in all motivational systems. ►Anxiety-related strain differences are unlikely to be secondary to cognition. ►Aversive stimulus shows primary characteristic of anxiety-related strain differences. ►Plasma Mg2+ levels are significantly correlated with anxiety-related parameters.