Dopamine (DA) neurons in the ventral tegmental area (VTA) help mediate stress susceptibility and resilience. However, upstream mechanisms controlling these neurons remain unknown. Noradrenergic (NE) neurons in the locus coeruleus, implicated in the pathophysiology of depression, have direct connections within the VTA. Here we demonstrate that NE neurons regulate vulnerability to social defeat through inhibitory control of VTA DA neurons.

1 In vitro studies have been performed on human medium-sized muscular arteries (internal diameter 1-4mm) in a classical organ bath and with human subcutaneous resistance arteries (internal diameter 103-626pjm) in a microvascular myograph. 2 Although the medium-sized muscular arteries showed no response to either of the x2-agonists B-HT 933 or UK 14304 in concentrations up to IO yM, the subcutaneous resistance arteries from all regions examined showed well-pronounced and concentration-dependent responses to B-HT 933, the pD2 (-log EC50) being 5.11 + 0.09.3 In the resistance arteries the Cc2-antagonist yohimbine caused a parallel shift to the right of the B-HT 933 concentration-response curve; the yohimbine pA2 for the B-HT 933 receptor was 7.86 + 0.12. 4 There was an inverse relationship between the maximum response to B-HT 933 and the calibre of the resistance vessels. 5 These results indicate the presence of a postjunctional a2-adrenoceptor in human subcutaneous resistance arteries and not in medium sized muscular arteries.

1. The role of the endothelium in mediating relaxation to acetylcholine, the calcium ionophore A23187, vasoactive intestinal peptide and peptide histidine methionine was studied using isolated human blood vessels. 2. Segments of renal, colic, pulmonary, uterine, transverse cervical, brachial, coronary and coeliac branch arteries, and saphenous veins, were obtained from surgical resection material for use in tissue bath studies. 3. Acetylcholine or A23187 produced endothelium-dependent relaxation in isolated vessels from all vascular beds studied. Coronary arteries, however, differed in their response to acetylcholine which produced predominantly a contractile response, either alone or after initial relaxation. 4. Vasoactive intestinal peptide and peptide histidine methionine produced endothelium-dependent relaxation in coeliac branch arteries. However, these peptides relaxed isolated pulmonary arteries independently of endothelium. 5. Endothelium-dependent relaxation in response to acetylcholine and A23187 was antagonized by nordihydroguaretic acid, a lipoxygenase inhibitor, and methylene blue and haemoglobin, inhibitors of soluble guanylate cyclase. In these respects the endothelium-dependent responses of human arteries to acetylcholine and A23187 resemble those described in other species.

1Human resistance arteries were obtained from specimens of omentum and subcutaneous fat removed at surgery. They were studied in vitro by use of a myograph technique to determine the effects of purines on the arteries.2 In preparations where tone had been raised with noradrenaline, low concentrations (1 nM-1 gM) of adenosine triphosphate (ATP) and 2-methylthioATP, but not a,,-methyleneATP, produced concentration-dependent relaxation. There was a lack of relationship between the relaxation response to acetylcholine and that to ATP. 3 In preparations under basal tone, high concentrations (1 piM-1 mM) of ATP, 2-methylthioATP and a4,-methyleneATP produced concentration-dependent contractions. 4 The rank order of potency of the purine nucleotide analogues for the relaxation response was 2-methylthioATP > ATP > a4-methyleneATP and for the contractile response it was x,,BmethyleneATP > ATP = 2-methylthioATP. 5 Adenosine produced concentration-dependent relaxation in preparations under raised tone and was less potent than ATP but did not produce contraction in preparations at basal tone. Relaxation responses to adenosine, but not to ATP, were antagonized by 8-phenyltheophylline.6 These results indicate the presence of vasodilator P2Y-and P1-purinoceptors and vasoconstrictor P21-purinoceptors on human resistance arteries isolated from omental and subcutaneous sites.

ABSTRACT. A number of studies have indicated that the emphasis on low shear rate viscosity and rouleaux-related pherheologic properties of neonatal blood are different from nomena. those of the adult. The frequent administration of blood components to the neonate during intensive care make it important that these differences be established and their MATERIALS AND METHODS causes understood. The purpose of this study was to make a detailed comparison of the rheologic properties of nee-Blood was obtained from healthy adults by venesection, natal and adult blood, with particular emphasis on low and from the umbilical vein of neonates immediately after shear rate viscosity and rouleaux-related phenomena. The clamping of the cord at delivery. In each case, it was anticoaguviscometric data was obtained from seven preterm (PT) lated with 12.5 U/mL of heparin. The babies were all born and l8 term (NT) babies and with those vaginally and did not require resuscitation. They were of normal l8 (A)-In the present study, "iscometry was wt for gestation age. There were too few preterm babies to group performed Over a wide range Of shear rates, O a 3 them according to gestational age, which ranged from 24 to 35 130 s-', and the low shear rate data were with wk, thus all babies of less than 37 wk were classified as preterm. direct measurement of rouleaux formation using the MY-he adults had an age range of 24 to 50 y with a median age of renne Erythrocyte Aggregometer. A major factor leading 30. to the viscometric differences observed was the high hem-1, a pilot survey, the rheologically important variables-hematOcrit in the newborn (46.8 + 2.1% PT, 52.8 + atocrit, plasma viscosity, and plasma fibrinogen concentration-6-1% NT, 44-1 * 2.5% A 40.5 + A females)-were compared between pre-and normal term babies and adults.ow ever, this tended to be compensated for by the lower This was followed by a more comprehensive hemorheologic plasma (Iso5 * 0.07 mPas PT, * 0-14 mPas study that included the measurement of blood viscosity over a NT,* O e o 8 mPas A-n0 sex difference) and reduced wide range of shear rates. These viscometric studies were made rOuleaux in the and more according to the ICSH Guidelines (7) on blood at native hemamarked in the preterm baby. The lowered levels red tocrit and, after adjustment by adding or subtracting autologous aggregation were found not to be due to cellular differences plasma, at 45%. The hematocrit was measured by microcentribetween the adults and the babies but rather to differing fugation without correction for trapped plasma, plasmaThe presence the fetal variant In some experiments, washed cells were used. The cells were fibrinogen and low levels of immunoglobulins, especially washed, by alternate centrifugation and aspiration of supernaIgM and IgA, are likely be particular imp0rtance. tant, using isotonic PBS. The cells were finally suspended at a (Pediatv Res 25457-460, 1989) hematocrit of 45% in PBS or PBS containing adult human fibrinogen (Kabi Pharmaceuticals, Stockholm, Sweden). Fibrinog...