Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D 2 receptor density in vivo in human striatum. 1 Low D 2 receptor binding in vivo has been found to associate with alcohol/substance dependence. [2][3][4][5][6] It has been suggested that the A1 allele of human D 2 receptor gene might be associated to a specific type of alcoholism 7 and possibly to a reduced D 2 receptor density in vitro. 8 We have determined D 2 dopamine receptor-binding density (B max ), affinity (K d ) and availability (B max /K d ) in 54 healthy Finnish volunteers using PET and [ 11 C]raclopride in order to determine whether the A1 allele is associated with a 'baseline' difference in D 2 receptor characteristics in vivo. A statistically significant reduction in D 2 receptor availability reflecting an alteration in receptor density was observed in the A1/A2 genotype group compared to the A2/A2 group. There was no difference in apparent K d between the two groups. In conclusion, the association between the A1 allele and low D 2 receptor availability in healthy subjects indicates that the A1 allele of the TaqIA polymorphism might be in linkage disequilibrium with a mutation in the promoter/regulatory gene element that affects dopamine D 2 receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers.The dopaminergic system plays a major role in the regulation of movement, hormone secretion, mood and various motivational behaviors related to reward and reinforcement. While the contribution of the dopaminergic system has frequently been implicated in the etiology of alcohol/drug dependence, the mechanisms underlying this have remained unclear. It has been suggested that genetic factors might contribute individual differences in the regulation of D 2 receptor density and liability for predisposition to alcohol/drug dependence. This is supported by recent positron emission tomography (PET) studies which have consistently demonstrated that alcohol, 2,3 cocaine 4,5 and opiate 6 abusers have lower striatal D 2 receptor availability in vivo compared to healthy volunteers. The molecular basis of the possible hereditary factors in the dopaminergic system affecting predisposition to alcohol/drug dependence have remained unknown. The three nucleotide substitutions causing alteration in amino acid sequence found in the coding region of the D 2 dopamine receptor gene have been revealed to be relatively rare 9 and without clear effect on the D 2 receptor function in vivo. 10 While some regulatory sequences and promoter regions have been identified for human D 1 , 11 D 5 12 and rat D 2 13-15 receptors within the 5′ flanking region, little is known about the molecular events that regulate the transcription of the human D 2 receptor. From the several polymorphic gene markers, the A1 allele of TaqIA RFLP within the D 2 receptor gene suggests association with a specific type of alcoholism. 7 Despite numerous case-control studies, 16 the role of the A1 al...

The mean ±s.e. optimum temperature (T(opt)) for aerobic scope in juvenile coho salmon Oncorhynchus kisutch was determined to be 17·0 ± 0·7° C. The repeated measures protocol took 3 weeks to complete the T(opt) determination using 12 fish tested at five temperatures separated by 2° C increments. This experiment also demonstrated that the T(opt) was associated with maximum heart rate (f(H)) failing to maintain a Q(10) -related increase with temperature. When maximum f(H) was produced in anaesthetized fish with pharmacological stimulation and f(H) measured from electrocardiogram recordings during acute warming, the Arrhenius break temperature (ABT) for Q(10) discontinuities in maximum f(H) (mean ±s.e. = 17·1 ± 0·5° C for 15 ppm clove oil and 16·5 ± 0·2° C for 50 ppm MS-222) was statistically indistinguishable from the T(opt) measured using aerobic scope. Such a determination took only 3 days rather than 3 weeks. Therefore, it is proposed that determining ABT for discontinuities in maximum f(H) in anaesthetized fish presents itself as a valuable, high-throughput screening tool to assess T(opt) in fishes, a metric that has become recognized as being extremely valuable in fish biology and fisheries management.

Anthropogenic environmental change is exposing animals to changes in a complex array of interacting stressors and is already having important effects on the distribution and abundance of species. However, despite extensive examination of the effects of stressors in isolation, knowledge of the effects of stressors in combination is limited. This lack of information makes predicting the responses of organisms to anthropogenic environmental change challenging. Here, we focus on the effects of temperature and hypoxia as interacting stressors in fishes. A review of the available evidence suggests that temperature and hypoxia act synergistically such that small shifts in one stressor could result in large effects on organismal performance when a fish is exposed to the 2 stressors in combination. Although these stressors pose substantial challenges for fish, there also is substantial intraspecific variation in tolerance to these stressors that could act as the raw material for the evolution of improved tolerance. However, the potential for adaptive change is, in part, dependent on the nature of the correlations among traits associated with tolerance. For example, negative genetic correlations (or trade-offs) between tolerances to temperature and hypoxia could limit the potential for adaptation to the combined stressors, while positive genetic correlations might be of benefit. The limited data currently available suggest that tolerances to hypoxia and to high-temperature may be positively correlated in some species of fish, suggesting the possibility for adaptive evolution in these traits in response to anthropogenic environmental change.

SUMMARYIn fishes, performance failure at high temperature is thought to be due to a limitation on oxygen delivery (the theory of oxygen and capacity limited thermal tolerance, OCLTT), which suggests that thermal tolerance and hypoxia tolerance might be functionally associated. Here we examined variation in temperature and hypoxia tolerance among 41 families of Atlantic salmon (Salmo salar), which allowed us to evaluate the association between these two traits. Both temperature and hypoxia tolerance varied significantly among families and there was a significant positive correlation between critical maximum temperature (CT max ) and hypoxia tolerance, supporting the OCLTT concept. At the organ and cellular levels, we also discovered support for the OCLTT concept as relative ventricle mass (RVM) and cardiac myoglobin (Mb) levels both correlated positively with CT max (R 2 =0.21, P<0.001 and R 2 =0.17, P=0.003, respectively). A large RVM has previously been shown to be associated with high cardiac output, which might facilitate tissue oxygen supply during elevated oxygen demand at high temperatures, while Mb facilitates the oxygen transfer from the blood to tissues, especially during hypoxia. The data presented here demonstrate for the first time that RVM and Mb are correlated with increased upper temperature tolerance in fish. High phenotypic variation between families and greater similarity among full-and half-siblings suggests that there is substantial standing genetic variation in thermal and hypoxia tolerance, which could respond to selection either in aquaculture or in response to anthropogenic stressors such as global climate change.

Increases in environmental temperature predicted to result from global warming have direct effects on performance of ectotherms. Moreover, cardiac function has been observed to limit the tolerance to high temperatures. Here we show that two wild populations of Atlantic salmon originating from northern and southern extremes of its European distribution have strikingly similar cardiac responses to acute warming when acclimated to common temperatures, despite different local environments. Although cardiac collapse starts at 21-23°C with a maximum heart rate of B150 beats per min (bpm) for 12°C-acclimated fish, acclimation to 20°C considerably raises this temperature (27.5°C) and maximum heart rate (B200 bpm). Only minor population differences exist and these are consistent with the warmer habitat of the southern population. We demonstrate that the considerable cardiac plasticity discovered for Atlantic salmon is largely independent of natural habitat, and we propose that observed cardiac plasticity may aid salmon to cope with global warming.

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The wide thermal tolerance range of a eurythermic fish (goldfish, Carassius auratus) was used to evaluate how temperature performance curves derived from maximum heart rate (fH) related to those for aerobic scope. For acclimation temperatures of 12°, 20°, and 28°C, optimum temperatures derived from aerobic scope curves (Topt) were 19.9° ± 0.4°, 19.3° ± 0.8°, and 28.7° ± 0.8°C, respectively. The Arrhenius breakpoint temperatures (TAB) for maximum fH were 21.5° ± 0.6°, 23.8° ± 0.9°, and 24.6° ± 0.5°C, respectively. The TQB (temperature where the incremental Q10 of maximum fH decreased abruptly below 1.9) was 24.0° ± 0.7° and 29.8° ± 0.6°C for the 12° and 28°C acclimation temperatures, respectively, and was within the Topt window (11.5°-30.3° and 26.9°-30.5°C, respectively), but TQB for the 20°C acclimation temperature (27.3° ± 0.6°C) was higher than the Topt window (15.4°-23.2°C). Warm acclimation increased the upper critical temperature (Tcrit; from 37.2° ± 0.7° to 44.7° ± 11.8°C) as well as the temperature that triggered a cardiac arrhythmia (Tarr; from 31.1° ± 0.7° to 39.3° ± 0.4°C). In conclusion, we propose that maximum fH and its associated rate transition temperatures (TAB, TQB, and Tarr) can be used to estimate the upper thermal tolerance of eurythermic as well as stenothermic fish independent of acclimation temperature. All the same, great care is needed with such evaluations. For the goldfish, while TAB and TQB were always within the Topt window for 90% of maximum aerobic scope and Topt was closely associated with TAB for 12°C-acclimated fish, TQB had the closest association after 28°C acclimation, and both TAB and TQB were above the Topt window after 20°C acclimation.

Temperature affects processes at all levels of biological organization, but it is unclear whether processes at different levels have similar thermal optima (T(opt)). Here, we compare the T(opt) for aerobic scope, a whole-organism measure of performance, with both the Arrhenius breakpoint temperature for maximum heart rate (HR-ABT), a measure of tissue level performance, and the temperature at which AMP-activated protein kinase (AMPK) is phosphorylated in the heart, an indicator of an increase in dependence on anaerobic energy metabolism at the cellular level in juvenile rainbow trout Oncorhynchus mykiss. The T(opt) for aerobic scope was 19°C, with aerobic scope being maintained at ≥90% of maximum (termed a "T(opt) window") from 16.5° to 20.5°C. HR-ABT occurred at [Formula: see text], while the profile of AMPK phosphorylation started to change from baseline at 19°C, suggesting that these processes have similar thermal sensitivities as a fish is warmed to T(opt). The effects of temperature on AMPK phosphorylation were also measured in coho salmon Oncorhynchus kisutch hearts and compared with previously published values for HR-ABT and aerobic scope T(opt). AMPK phosphorylation in coho hearts began to change at temperatures above 17°C, which again is comparable with the published T(opt) for aerobic scope (17°C) and HR-ABT ([Formula: see text]) in these individuals. Thus, the thermal sensitivity of these subcellular, tissue, and whole-organism functions are highly correlated in both rainbow trout and coho salmon and may depend on each other.