J. Harro et al., Chronic mild unpredictable stress after noradrenergic denervation: attenuation of behavioural and biochemical effects of DSP-4 treatment, EUR NEUROPS, 10(1), 1999, pp. 5-16
Chronic mild unpredictable stress, which reduces rewarded behaviour in rats
: is becoming increasingly popular as an animal model of depression. The ef
fect of chronic mild stress (applied to animals housed five per cage for 15
days) on forced swimming and open field behaviour, and on beta-adrenocepto
r 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 swim
ming test, chronic mild stress reduced the immobility time on the second da
y 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 (b
ut caused a reduction in defecations), but completely blocked the DSP-4-ind
uced decrease in the exploratory activity. As measured by H-3-dihydroalpren
olol binding, DSP-4 treatment increased the P-adrenoceptor affinity in the
frontal cortex and the number of binding sites in the hippocampus and in th
e cerebral cortex (total-frontal cortex). Stress had no effect on the P-adr
enoceptor binding in the frontal cortex and cerebral cortex, but prevented
the increase in affinity caused by DSP-4 treatment in the frontal cortex. I
n the hippocampus, chronic mild stress and DSP-4 treatment increased the nu
mber of P-adrenoceptor binding sites. Neither chronic mild stress nor DSP-4
treatment had any effect on CCK, receptor binding in the cerebral cortex a
nd striatum. These results show that chronic mild stress applied to group-h
oused rats can prevent the development of certain behavioural and biochemic
al changes caused by the denervation of the locus coeruleus projection area
s. (C) 1999 Published by Elsevier Science B.V. All rights reserved.