Hypertension and insulin resistant models have divergent propensities to learned helpless behavior in rodents

The induction of learned helpless (LH) behavior in rats is a widely used mo del of unipolar depression. Recent studies have linked depression with hype rtension and insulin resistance as observed in obesity, but the propensity of these disorders to manifest depression has not been reported. In this st udy, the LH behavioral paradigm was exploited in a model of hypertension (D ahl rat) and of insulin resistance (Zucker rat) to determine the propensity of these models to develop depression and to examine the profile of marker s for the propensity of the cardiovascular system (plasma renin activity) a nd of the hypothalamus-pituitary-adrenal axis (corticosterone) in the displ ay of propensity to depression. Results show that Zucker rats displayed the lowest propensity to the development of LH behavior (12%), followed by the control Sprague-Dawley rats (27%), and then Dahl rats (66%). In contrast, congenital learned helpless (cLH) rats, a genetically bred strain for anima l depression, had the highest propensity (>90%). A gender effect was observ ed in the Zucker and cLH rats, with females showing an increased propensity to develop LH behavior. Plasma renin activity in the Dahl and Sprague-Dawl ey rats after the LH stress paradigm was not significantly different from b aseline. In contrast, Zucker rats, with the lowest propensity to LH behavio r, demonstrated a threefold increase in plasma renin activity after stress. Congenital LH rats, with the highest propensity to LH behavior, exhibited a significantly lower increase (43%) in plasma renin activity after stress. Hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis functioning corre lated with propensity of LH behavior. Stress-induced corticosterone levels increased under twofold in cLH rats, whereas they increased more than seven fold in Zucker rats. Taken together, these studies suggest that whereas gen etically prone hypertensive rats have a very high propensity to depression, insulin-resistant rats have a profound resistance to depression. Moreover, a hyporesponsive HPA axis may be a marker for disorders that are comorbid with depression, whereas a hyperresponsive renin-angiotensin system may be indicative of resilience. Am J Hypertens 2000;13:659-665 (C) 2000 American Journal of Hypertension, Ltd.