THE HABITUATION OF BRAIN-STEM CATECHOLAMINERGIC GROUPS TO CHRONIC DAILY RESTRAINT STRESS IS STRESS SPECIFIC LIKE THAT OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS

It has previously been shown that immobilization and ether stress indu ce activation of the hypothalamo-pituitary-adrenal (HPA) axis and that this activation occurs subsequent to activation of brain stem catecho laminergic neurones. In the present study we have investigated whether the brain stem catecholaminergic (CA) neurons show habituation to chr onic daily intermittent exposure to the same restraint stress comparab le to that of the HPA axis. The level of activity of the brainstem CA groups was estimated by measurement in tissue punches of content of 3, 4-dihydroxyphenylacetic acid (DOPAC), a side metabolite of noradrenali ne and adrenaline biosynthesis which has been shown to be a reliable i ndex of the stress-induced activation of the CA groups. The level of a ctivity of the HPA axis was determined by measurement of plasma cortic osterone and adrenocorticotropic hormone (ACTH) levels. The animals we re submitted to a 15 min restraint stress daily. They were sacrified a t the end of the stress session on day 3, 5 and 10. The ACTH response to the acute restraint stress whilst unchanged on day 3 was significan tly decreased on day 5 (-54%) and day 10 (-70%) compared to the respon se in naive rats. The approximately twofold increase in DOPAC level in duced by acute restraint stress in the so-called CA medullary group A1 /C1 of naive rats was reduced in daily restraint rats on day 5 (-22%) and day 10 (-30%) but was unchanged on day 3. A small (-20%) decrease of the stress-induced DOPAC response in the A2/C2 CA group and locus c oeruleus was also observed on day 10. In animals submitted to four dai ly sessions of restraint stress, the increase in ACTH response to a no vel (ether) stress was not reduced but rather was enhanced by 30% as c ompared to the response obtained in naive rats. Similarly the DOPAC re sponse in the A1/C1 group to an acute ether stress was enhanced by 25% in chronically stressed animals while the DOPAC response in the A2/C2 group and the locus coeruleus were unchanged. Our present data indica te that brain stem CA group show habituation to chronic intermittent s tress. Habituation of the A1/C1 group and habituation of HPA axis have similar time-courses and are similarly stress-specific. The latter re sults suggest that habituation observed in these experimental conditio ns is not due to intrinsic biochemical changes in the brain stem CA ne urones but indirectly reflects decreased stimulatory inputs to the bra in stem CA groups resulting from behavioural adaptation at higher brai n centers.