The mesocorticolimbic dopamine (DA) system is implicated in neurodevelopmental psychiatric disorders including schizophrenia but it is unknown how disruptions in brain development modify this system and increase predisposition to cognitive and behavioural abnormalities in adulthood. Netrins are guidance cues involved in the proper organization of neuronal connectivity during development. We have hypothesized that variations in the function of DCC (deleted in colorectal cancer), a netrin-1 receptor highly expressed by DA neurones, may result in altered development and organization of mesocorticolimbic DA circuitry, and influence DA function in the adult. To test this hypothesis, we assessed the effects of reduced DCC on several indicators of DA function. Using in-vivo microdialysis, we showed that adult mice that develop with reduced DCC display increased basal DA levels in the medial prefrontal cortex and exaggerated DA release in response to the indirect DA agonist amphetamine. In contrast, these mice exhibit normal levels of DA in the nucleus accumbens but significantly blunted amphetamine-induced DA release. Concomitantly, using conditioned place preference, locomotor activity and prepulse inhibition paradigms, we found that reduced DCC diminishes the rewarding and behavioural-activating effects of amphetamine and protects against amphetamine-induced deficits in sensorimotor gating. Furthermore, we found that adult DCC-deficient mice exhibit altered dendritic spine density in layer V medial prefrontal cortex pyramidal neurones but not in nucleus accumbens medium spiny neurones. These findings demonstrate that reduced DCC during development results in a behavioural phenotype opposite to that observed in developmental models of schizophrenia and identify DCC as a critical factor in the development of DA function.
A hot and humid environment can be detrimental to race performance. Caffeine, on the other hand, has been shown to be an ergogenic aid for improving endurance performance. To examine the influence of caffeine ingestion on race performance during high heat stress, seven endurance trained competitive road racers aged between 23 and 51 years (five men, two women) performed three maximal effort 21-km road races outdoors in hot and humid conditions. The caffeine dose, randomly assigned in a double-blind fashion, consisted of either 0, 5, or 9 mg.kg-1 body mass. During each run, the subjects were allowed to drink water ad libitum at each 5-km point. Blood samples were obtained immediately before and after each run and analysed for changes in concentrations of Na+, K+, glucose, lactate, and hematocrit. Pre and postrun data were also collected for body mass and tympanic membrane temperature. Race times were not significantly different among the races or caffeine doses, with the average times within 1.1% of each other. In addition, none of the other variables measured varied significantly among the races or caffeine doses. In summary, caffeine intake did not affect race performance. Therefore it was concluded from our study that caffeine is not of ergogenic benefit in endurance races during high heat stress.
To determine the impact of creatine supplementation on high-intensity, intermittent work, 18 participants each performed 2 sets of 4 different work bouts to exhaustion. For 5 days prior to the first set of work bouts, all participants received a placebo (5 g of calcium chloride daily). For the second set of work bouts, 9 participants again received the placebo, while the other 9 received creatine supplementation (18.75 g creatine monohydrate daily for 5 days prior to and 2.25 g creatine daily during testing). The four work bouts in each set consisted of cycling to exhaustion at 150% peak oxygen uptake (VO2peak) either nonstop (A), intermittently for either 60-s work/120-s rest periods (B), 20-s work/40-s rest (C), or 10-s work/20-s rest (D). Creatine supplementation significantly increased (p < .01) the total work time of all bouts. Protocol D showed the greatest increase (> 100%); C increased 61.9%; B increased 61.0%; and A increased 23.5%. These results demonstrate that creatine supplementation significantly extends one's capacity to maintain a specific level of high-intensity, intermittent exercise.
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