Pregnancy changes physiological responses to stress, including attenuation of the hypothalamo-pituitary-adrenal (HPA) axis. This results, at least in part, from opioid inhibition of the central noradrenergic input to the HPA axis1,2, and during the last trimester may protect the foetus from adverse effects of glucocorticoids and stabilise metabolism of the mother and foetus. Although sympathetic and adrenal medulla responses to stress are important for the fight or flight response and immediately elevate glucose availability, their responses during pregnancy are poorly understood. We studied the hypothesis that sympathetic responses are attenuated in late pregnancy. During stress enkephalin is synthesised and secreted from chromaffin cells into blood and may mediate neuroendocrine, cardiovascular and immune functions; so we also measured adrenal medulla enkephalin responses. Virgin and 21 day pregnant rats were blood sampled via a previously implanted jugular cannula before and after exposure to airpuff startle stress3 in their home cages (n=8,6, respectively); control groups were not stressed (n=7,6, respectively). Plasma samples were analysed for ACTH, adrenaline and noradrenaline by RIA. Rats were killed at 90 min and the adrenal medulla was assayed for enkephalin content4. Data are mean±S.E.M. Airpuff startle increased ACTH secretion at 10 min in virgin but not pregnant rats as expected. Airpuff also significantly increased adrenaline secretion at 2.5 min in virgin but not pregnant rats (to 3031±933 and 1684±205 pg/ml, respectively; 3way ANOVA, interaction across treatment, group and time p<0.05); controls did not significantly change. Delta noradrenaline secretion was 2146±722 pg/ml in stressed virgins and was not significantly different in stressed pregnant rats (1816±834 pg/ml). This indicates that although adrenaline secretory responses are attenuated, peripheral noradrenergic responses remain intact. Adrenal gland weight was not significantly altered during pregnancy (37.5±2.1 vs 38.3±1.3 mg in virgins) or by the stress exposure. Adrenal medulla enkephalin content was not significantly altered in pregnancy (7.5±1.1 vs virgins 4.9±0.5 pmol/g). Airpuff startle increased enkephalin content in virgin rats (to 11.0±1.8 pmol/g) but not in pregnant rats (to 5.5±0.6 pmol/g, 2 way ANOVA interaction group x treatment p<0.01), suggesting that enkephalin peptide processing increases in response to stress in virgin but not in pregnant rats. In conclusion, the data show that adrenaline and medulla responses to stress are attenuated in late pregnancy but peripheral noradrenaline responses, reflecting sympathetic activity, are not. Both mechanisms may help protect the pregnancy: attenuated adrenaline responses preventing sudden fluctuations in glucose availability and heart rate and the retained sympathetic responses allowing the mother to respond appropriately to threat. Reference 1 : Douglas AJ, et al (2005) J Neuroendocrinol 17:40-48.Reference 2 : Brunton PJ, et al (2005) J Neurosci 25(21):5117-5126.Reference 3 : Neumann ID, et al (2003) Endocrinology 144(6):2473-9Reference 4 : Pierzchala K and Van Loon GR (1990) J Clin Invest 1990, 85, 861-873.