Met-enkephalin, injected during the early phase of stress, attenuates stress-induced increases in noradrenaline release in rat brain regions.

By measuring levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of noradrenaline (NA), we investigated the effects of Met-enkephalin (Met-ENK) ICV injected at three different stages of stress, i.e., 0 min, 5 min, or 10 min after exposure to immobilization stress. Immobilization stress caused significant increases in MHPG-SO4 levels in all brain regions examined, i.e., the hypothalamus, amygdala, thalamus, midbrain, hippocampus and locus coeruleus (LC), which suggests that stress increases NA release in these regions. Met-ENK at a dose of 50 micrograms, injected ICV immediately before stress exposure significantly attenuated stress-induced increases in MHPG-SO4 in the amygdala, thalamus and LC, but did not have such an effect when injected either 5 min or 10 min or 10 min after exposure to stress. Similarly, Met-ENK at 150 micrograms at 0 min significantly attenuated these increases in all brain regions examined, however, it did not do so when given at 5 min or 10 min after stress initiation. The amount of defecation and the weight loss caused by stress were also significantly attenuated by Met-ENK injected but only at 0 min. These results suggest that the attenuating effect of Met-ENK on stress-induced increases in NA release is greatly affected by the time of the peptide administration and that Met-ENK might inhibit stress-induced increases in NA release in these regions by affecting the initial changes induced by stress.