The proposed experiments will investigate the relationship of brain aldosterone binding angiotensinogen gene expression to control of a model motivated behavior (salt consumption) and a regulated physiological process (the circulation). Genetic influences on these processes will be studied through analysis of phenotype variation in behavior, physiology and neuroendocrinology subsequent to selective inter- and intra-strain breeding homozygous rats with well characterized behavioral and cardiovascular phenotypes. After accurately describing differences between homozygous salt avid/high blood pressure and salt avoiding/low blood pressure rats in binding of aldosterone and expression of angiotensinogen messenger RNA in brain, subgroups of the segregating F2 descendants of these inbred strains will be selected, based on extremes of slat appetite and blood pressure, for a genetic analysis of linkage among these traits. Covariation between selected salt appetite or blood pressure phenotypes and neuroendocrine measures in the F2 population will provide evidence for genetic linkage, whereas independent assortment of phenotypes will support an interpretation of no genetic linkage. Additional experiments will examine strain differences in the development of aldosterone binding and Ao gene expression in the brain, relative to the development of salt appetite and blood pressure. The development analyses can provide support for neuroendocrine mediation of either the behavioral or cardiovascular phenotype by evaluating the temporal relationship between changes in aldosterone binding or Ao gene expression and the traits to which they are linked. The mental health relevance of the proposed research derives from the insights that it will provide genetic and development influences on motivated behavior, circulatory control and possible neuroendocrine mechanisms through which these influences are mediated.
| Yongue, B G (1993) Strategies for investigation of CNS mechanisms of phenotypic variation in blood pressure and salt appetite in genetic hypertensive rats. Steroids 58:594-604 |
