Consumption of a high n-3 polyunsaturated fatty acid diet during gradual mild physiological stress in rats.

n-3 Polyunsaturated fatty acids (n-3PUFAs) may be beneficial for anxiety and depression under stressful conditions. Studies however, typically utilise physical or sudden physiological stress, while gradual physiological stress is also relevant to human conditions. Using deoxycorticosterone acetate (DOCA) administration to induce gradual physiological stress, this study investigated the impact of n-3PUFAs under gradual physiological stress in rats. Animals (aged 2 months) (N=8-12/group) received daily injections of DOCA or vehicle and were concurrently fed a high n-3PUFA or control diet for eight weeks. Behavioural measures were taken throughout. Behavioural tests and physiological measures were conducted after six and eight weeks respectively. DOCA administration decreased plasma renin, plasma proteins and relative adrenal weight, and increased water intake, relative kidney weight, and anxiety in the open field. These findings demonstrate disruptions to the renin-angiotensin-aldosterone system, a result of mild physiological stress, that also impact on anxiety behaviours. No effects of n-3PUFAs were found.

Social defeat and isolation induce clear signs of a depression-like state, but modest cardiac alterations in wild-type rats.

Adverse social environments play a relevant role in the onset and progression of mood disorders. On the other hand, depression is an independent risk factor for cardiovascular morbidity. This study was aimed at (i) corroborating the validity of a rat model of depression based on a negative social episode followed by social isolation and (ii) verifying its impact on cardiac function and structure. Pair housed, wild-type Groningen rats (Rattus norvegicus) were implanted with radiotransmitters for ECG, temperature and activity recordings. They were either exposed to a social defeat episode followed by 4-week isolation or left undisturbed with their female partners. The social challenge induced a series of biological changes that are commonly taken as markers of depression in rats, including decreased body weight gain and reduced preference for sucrose consumption, functional and structural changes of the hypothalamic-pituitary-adrenocortical axis, increased anxiety in the elevated plus maze test. The cardiovascular alterations consisted in (i) transitory heart rate circadian rhythm alterations, (ii) lack of habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) to an acute stressor, and (iii) moderate hypertrophy affecting the right ventricle of the heart. These results indicate that a depression-like state induced via this model of social challenge was associated with a few modest cardiovascular changes. Further studies are required to confirm the validity of this rat model of depression as a valid preclinical approach to the comprehension of the biological substrates underlying depression-cardiovascular comorbidity.

Sadness and broken hearts: neurohumoral mechanisms and co-morbidity of ischemic heart disease and psychological depression.

Heart disease and depression are highly co-morbid. Clinical and experimental research over the past 70 years has led to several neurohumoral hypotheses of causative factors present under the conditions of either heart failure or of psychological depression. Some of these hypothesized factors are common to both disorders and are therefore attractive candidates to account for the high incidence of co-occurrence of depression and heart disease. One experimental approach to study the co-morbidity of heart failure and depression has been to study the behavioral, biochemical and physiological changes in a chronic mild stress model of depression and in heart failure induced by experimental myocardial infarction. Our studies have led us to focus on the pro-inflammatory cytokines, in particular tumor necrosis factor (TNF)-alpha, and the renin-angiotensin-aldosterone system. Both of these families of humoral factors are elevated in human heart failure and in depression and the two experimental models we have studied. The demonstrated validity of each of these models will be of great value in elucidating the nature of the actions and interactions of these humoral agents as they contribute to the co-morbid conditions of heart failure and depression.