Social interaction increases the extracellular levels of [MET]enkephalin in the nucleus accumbens of control but not of chronic mild stressed rats

Chronic application of various mild stress has been shown to decrease the responsiveness to reward in rats. This effect, which was suggested to mimic anhedonia, one of the main symptoms observed in depressive patients, can be measured by various tests. Thus chronic mild stress was shown to reduce the consumption of a palatable sucrose solution, and to decrease the acquisition of preferences for a distinct environment paired with a variety of reinforcing substances. These negative responses could be prevented by chronic treatment with tricyclic or atypical antidepressants. The behavioural changes, induced by exposure to chronic mild stress, were shown to be associated with a number of changes in dopaminergic neurotransmission in the mesolimbic system, especially in the nucleus accumbens. The nucleus accumbens contains a large number of enkephalinergic cell bodies giving rise to local collaterals and axons projecting to the globus pallidus-ventral pallidum region (for review see Ref. 9). Furthermore, there is evidence that this structure is instrumental in mediating the reward effects of exogenous and endogenous opioids (for reviews see Refs 5,7,17). This study was carried out to analyse the possible contribution of the enkephalinergic system in the anhedonic-like state induced by chronic mild stress. Microdialysis was used to study the extracellular levels of [Met]enkephalin-like material in the rostral part of the nucleus accumbens of freely moving rats exposed or not to chronically mild stress. In both groups, the basal levels of [Met]enkephalin-like material were found to be similar. Exposure of the two groups to a congener, increased the extracellular levels of [Met]enkephalin in the controls but not in chronic mild stressed rats. This suggests that the reactivity of the endogenous opioid system could be reduced in stress induced model of anhedonia.