Selective breeding for helplessness in rats alters the metabolic profile of the hippocampus and frontal cortex: a 1H-MRS study at 9.4 T.

In humans metabolic changes, particularly in frontal areas of the brain, accompany depressive disorders, but few studies were conducted in animal models of depression. We used hydrogen-1 magnetic resonance spectroscopy at 9.4 T to measure the metabolic profiles of the hippocampus and frontal cortex in congenital learned helpless (cLH) and wild-type (WT) rats. The learned helplessness model of depression exposes animals to uncontrollable stress to induce changes in emotion, cognition and behaviour, but cLH rats were selectively bred to show changes in behaviour even without exposure to uncontrollable stress. Experimentally naive male 8- to 10-wk-old cLH (n = 10) and WT rats (n = 22) underwent spectroscopy and were exposed to uncontrollable stress 1 wk after the scan. We found that cLH compared to WT rats had lower levels of glutamate in the hippocampus and lower levels of choline-containing compounds in the hippocampus and frontal cortex, but higher levels of taurine and phosphocreatine in these regions, pointing to compensatory efforts of the brain to reduce excitotoxic potential and to increase neuroprotection and energy, possibly as a result of cellular stress and damage. The reduction in choline-containing phospholipids might represent a source or correlate of such stress. Overall, the results indicate that metabolic abnormalities are present in animals with a predisposition to helplessness even without exposure to explicit stress and may help identify non-invasive biomarkers in individuals who are prone to depression.