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The "ups and downs" of signaling cascades in addiction.

Drug addiction is a chronic disease characterized by compulsive drug use despite the severe negative consequences associated with it. Repeated exposure to drugs of abuse results in molecular adaptations in neuronal signaling pathways, which eventually manifest in the complex behavioral alterations that characterize addiction. These include tolerance, sensitization, dependence, drug craving, and relapse. In this Review, we focus on recent studies highlighting signaling cascades initiated by cocaine, as a representative of a drug of abuse with a defined site of action, and alcohol, as a drug with an undefined primary site of action. Specifically, we describe recent studies that emphasize the role of protein-protein interactions, phosphorylation, and compartmentalization in the molecular mechanisms that result in the cellular and behavioral adaptations that underlie addiction. Signaling cascades that contribute to addiction, as well as those that protect or delay the development of addiction, are presented.

Alcoholism↗

Reduction of exercise-induced asthma in children by short, repeated warm ups.

AIM: To study the effect of a warm up schedule on exercise-induced asthma in asthmatic children to enable them to engage in asthmogenic activities. METHOD: In the first study, peak flows during and after three short, repeated warm up schedules (SRWU 1, 2, and 3), identical in form but differing in intensity, were compared in 16 asthmatic children. In the second study the efficiency of the best of these SRWU schedules was tested on 30 young asthmatic children. Children performed on different days a 7 minute run alone (EX1) or the same run after an SRWU (EX2). RESULTS: The second study showed that for most children (24/30) the fall in peak flow after EX2 was less than that after EX1. The percentage fall in peak flow after EX2 was significantly correlated with the percentage change in peak flow induced by SRWU2 (r = 0.68). The children were divided into three subgroups according to the change in peak flow after SRWU2: (G1: increase in peak flow; G2: < 15% fall in peak flow; G3: > 15% fall in peak flow). Only the children in the G3 subgroup did not show any gain in peak flow after EX2 compared with EX1. CONCLUSION: The alteration in peak flow at the end of the SRWU period was a good predictor of the occurrence of bronchoconstriction after EX2. An SRWU reduced the decrease in peak flow for most of the children (24/30) in this series, thus reducing subsequent post-exercise deep bronchoconstriction.

Adolescent↗