Chronic mild unpredictable stress after noradrenergic denervation: attenuation of behavioural and biochemical effects of DSP-4 treatment

Abstract

Chronic mild unpredictable stress, which reduces rewarded behaviour in rats, is becoming increasingly popular as an animal model of depression. The effect of chronic mild stress (applied to animals housed five per cage for 15 days) on forced swimming and open field behaviour, and on β-adrenoceptor binding was studied in naive rats and after the denervation of the locus coeruleus projections by DSP-4 (50 mg kg −1) treatment. In the forced swimming test, chronic mild stress reduced the immobility time on the second day of testing in both vehicle- and DSP-4-treated rats, indicating rather an antidepressant-like effect. This antidepressant-like effect of chronic mild stress in the forced swimming test was not present in individually housed rats which suggests that this paradigm is sensitive to housing conditions. Stress had no clear effect on the open field locomotion in naive animals (but caused a reduction in defecations), but completely blocked the DSP-4-induced decrease in the exploratory activity. As measured by 3H-dihydroalprenolol binding, DSP-4 treatment increased the β-adrenoceptor affinity in the frontal cortex and the number of binding sites in the hippocampus and in the cerebral cortex (total-frontal cortex). Stress had no effect on the β-adrenoceptor binding in the frontal cortex and cerebral cortex, but prevented the increase in affinity caused by DSP-4 treatment in the frontal cortex. In the hippocampus, chronic mild stress and DSP-4 treatment increased the number of β-adrenoceptor binding sites. Neither chronic mild stress nor DSP-4 treatment had any effect on CCK B receptor binding in the cerebral cortex and striatum. These results show that chronic mild stress applied to group-housed rats can prevent the development of certain behavioural and biochemical changes caused by the denervation of the locus coeruleus projection areas.