Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression.

Components of the brain's dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35-P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc), and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence.

Respiratory syncytial virus illnesses in human immunodeficiency virus- and noninfected children.

Respiratory syncytial virus (RSV) lower respiratory tract and febrile upper respiratory tract illnesses were prospectively assessed in cohorts of 83 infants born to human immunodeficiency virus (HIV)- and of 48 infants born to non-HIV-infected mothers. Of the infants born to HIV-infected mothers, 18 were themselves infected with HIV, 26 were indeterminant and 39 were free from HIV. Ten RSV illnesses occurred in 8 HIV-infected, 2 illnesses in 2 indeterminant and 17 illnesses occurred in 17 non-HIV-infected children. RSV shedding was prolonged in HIV class P2- vs. non-HIV-infected children, at medians of 30 days (range, 1 to 199 days) and 6 days (range, 1 to 21 days), respectively (P = 0.02). Ribavirin and intravenous immunoglobulin failed to eradicate RSV from one child who shed virus for 199 days. Wheezing occurred in 1 of 4 vs. 9 of 10 episodes of lower respiratory tract illness in HIV-infected and non-HIV-infected children, respectively (P = 0.04). No differences were noted in duration of illness, temperature, respiratory rate or oxygen saturation between HIV- and non-HIV-infected children. Infection control and public health concerns regarding prolonged shedding of RSV in HIV-infected children must be recognized.

Effect of prostaglandin E1 on blood flow in normal and ischemic canine hindlimbs.

Prostaglandin E1 (PGE1) is a potent vasodilator that will increase peripheral blood flow. After infusion of PGE1, little is known about the distribution of flow between skin and muscle or the effect of PGE1 on an ischemic leg. We infused intra-arterially PGE1 (5 ng/kg/min) into normal and ischemic canine hindlimbs. Radioactive microspheres were used to measure nutrient flow to skin and muscle and flow shunted through arteriovenous connections. Intra-arterial PGE1 caused significant increases in skin blood flow in both normal and ischemic hindlimbs. Shunted flow did not increase. Muscle flow increased in normal canine hindlimbs, but this increase was prevented by femoral artery ligation. We conclude that PGE1 increases absolute nutrient flow rather than opening arteriovenous shunts in the canine hindlimb. Skin flow is most sensitive to prostaglandin infusion. Muscle flow is increased in normal but not ischemic limbs. PGE1 may be useful in situations where vasospasm is a prominent feature. The role of PGE1 in atherosclerotic ischemic disease remains unclear.