Acute dosing

The single acute dose method can be applied to whole plasma studies if the dose can be discriminated from the endogenous background. Discrimination... 

NOTE The resident mouse was adminstered an acute dose of amphetamine 30 minutes before confrontation. Frequency of attacks is minute-by-minute average. 

Schirring, E., and Hecht, A. Behavioral effects of low, acute doses of (/-amphetamine on the dyadic interaction between mother and infant vervet monkeys (Cercopithecus aethiops) during the first six postnatal months. Psychopharmacology 64 219-224. 1979. 

A variety of factors differentiating tolerance studies could have contributed to the observed discrepancy. Lower doses are less likely to lead to tolerance than higher doses or will do so less rapidly. The habitual coffee drinkers in some studies may have had different levels or durations of consumption. In the cases of acute dosing, caffeine consumed by subjects outside the laboratory on the day of the experiment may have varied. This is particularly true when some investigators request in advance that subjects abstain from caffeine prior to the experiment, while others do not. Differences in age, gender, and arousal-relevant personality dimensions,... 

Hasenfratz, M., Battig, K., Acute dose-effect relationships of caffeine and mental performance, EEG, cardiovascular and subjective parameters. Psychopharmacology 114(2), 281-287, 1994. 

Zahn, T. and Rapoport, J., Autonomic nervous system effects of acute doses of caffeine in caffeine users and abstainers. Int J Psychophslol 5, 33-41, 1987. 

Summarize the acute neurochemical and behavioural effects of acute doses of amphetamine and cocaine. 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

Rigney U, Kimber S and Hindmarch I (1999). The effects of acute doses of standardised Ginkgo biloba extract on memory and psychomotor performance in volunteers. Phytotherapy Research, 13, 408 415. 

Scholey AB and Kennedy DO (2002). Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax Ginseng and their combination in healthy young volunteers Differential interactions with cognitive demand. Human Psychopharmacology - Clinical and Experimental, 17, 35-44. 

Beagles, prenatal and early neonatal stages, given single acute dose of 0.2-1.0 Gy, then observed over 11-year life span Irradiation at all ages was associated with increased risk of decreased fertility inhibited growth and development lower brain weight and increase in fatal neoplasms 5... 

Chinese hamster, Cricetus sp. ovary cells, single acute dose ranging between 0.005 and 0.06 Gy Increased frequency of sister chromatid exchange at 0.005 Gy increased numbers of chromosomal aberrations at >0.02 Gy no significant increase in cell death 10... 

Females, single acute dose of 0.25-6.5 Gy, observed over a 17-year postexposure period At doses >2 Gy, 53% developed endometriosis (abnormal uterine growth) vs. 26% in controls irradiated monkeys weighed 43% less than controls, 35% were anorexic, 89% had abnormal uterine anatomy, and histopathology in most tissues exceed 50% frequency 21... 

Singing vole, Microtus miurus 8.46 Gy, single acute dose LD50, 30 days after exposure 26... 

In some circumstances such as may be encountered after a terrorist attack, acute doses may be more important than potential chronic effects. More specifically, high doses of radiation may be immediately dangerous to life and health and could lead to severe injury including sickness, irreparable tissue damage, and death, although the more severe effects would likely only be observed after a nuclear explosion. For the purpose of this discussion, acute exposures are defined as those that occur in a relatively short time (over several days or less) and result in a dose of at least 25-35 rad (0.25-0.35 Gy).6-7... 

Specific health effects resulting from an acute dose appear only after the victim exceeds a dose threshold. That is, the health effect will not occur if doses are below the threshold. (Note that this is significantly different from the LNT model used to predict stochastic effects.) After reaching the acute dose threshold, a receptor can experience symptoms of radiation sickness, also called acute radiation syndrome. As shown in Table 3.2, the severity of the symptoms increases with dose, ranging from mild nausea starting around 25-35 rad (0.25-0.35 Gy) to death at doses that reach 300-400 rad (3-4 Gy). Table 3.2 shows that the range of health effects varies by both total dose and time after exposure. 

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