Differential Early Time Course Activation of the Brainstem Catecholaminergic Groups in Response to Various Stresses

Abstract

The effects of various stressors (restraint, ether, histamine and insulin-induced hypoglycemia stress) on the early time course activation of the different catecholaminergic (CA) cell groups A1/C1, A2/C2 and locus ceruleus (LC) from the brainstem were studied. The activity of the central noradrenergic neurons was assessed by measuring in tissue punches the 3,4-dihydroxyphenylacetic acid (DOPAC) level, a side metabolite of noradrenaline (NA) and adrenaline biosynthesis that is thought to reflect the activity of NA cells. Short 5 min restraint stress led to an immediate increase of DOPAC level in the three CA groups. In the A1/C1 and A2/C2 groups the maximal increase, respectively + 75 and + 50%, was already reached at the end of the application of the stress while for the LC the maximum (+84%) was obtained 15 min after the onset of the stress. Return to baseline level was achieved within 2 h. Continuous immobilization stress did not further alter the DOPAC concentration in the LC and the Al/Cl while a progressive increase up to 85% in the A2/C2 group was seen over 20 min. Following a 2-min exposure to ether, DOPAC was increased in all three structures within 5 min. At this time the maximum was already reached in the A1/C1 and LC, respectively +99 and +43%. After histamine or insulin injection DOPAC level increased in the A1/C1 and A2/C2 in the +25/+50% range but was not significantly affected in the LC. In all the stress situations studied the increase in DOPAC level, particularly in the Al/Cl group always preceded or was concomitant to the increase of plasma corticosterone. While our results confirm the well-known increase of the activity of the CA neurons following stress, they reveal clear-cut differences in the time course of the early activation as well as in the sensitivity of the various brainstem CA groups for different stressors. The rapid response and maximum amplitude which could be seen within 5 min is compatible with the hypothesis that the CA cells could be involved in the stimulation of the hypothalamic-pituitary-adrenal axis elicited by the stressors.