Todd T. Gleeson

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here, we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force, and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation.

The effects of training and captivity on the metabolic capacity of the lizardSceloporus occidentalis

SummaryThe effects of training and captivity on the running performance and selected metabolic and biochemical variables were investigated in the lizardSceloporus occidentalis (Sauria: Iguanidae) in two studies of 6 and 8 weeks duration. Resting and maximal oxygen consumption, lactate concentration of the blood and whole body, and enzyme activities in skeletal muscle were compared among trained and untrained-captive animals taken recently from the field. No significant changes in these metabolic and biochemical measurements occurred as a result of training or of captivity. Distance run to exhaustion and the running endurance of these animals also failed to change in a way attributable to the experimental treatments. Training and captivity appear incapable of altering the maximal rates or the components of metabolic energy production inS. occidentalis. This inflexibility is in contrast to the adaptability and plastic nature of the metabolic capacities exhibited by captive and domestic mammals subjected to varying amounts of chronic activity.

Foraging and Transport Costs in the Galapagos Marine Iguana, Amblyrhynchus cristatus

Metabolic rates of walking and swimming marine iguanas (Amblyrhynchus cristatus) were measured in order to evaluate the locomotory specialization of this submarine foraging lizard. These data are compared to similar data for walking Galapagos land iguanas (Conolophus subcristatus) and to data for other lizards. Juvenile (mass = 500 g) and adult (mass = 2,900 g) marine iguanas could sustain walking speeds of ≤1 km/h aerobically for at least 20 min at basking temperatures of 35 C. V̇o2 increased linearly with increased walking speed. Amblyrhynchus studied in the field walked at 0.8-1.0 km/h, but were capable of brief bursts in excess of 9.0 km/h. Adaptation to swimming has not resulted in increased transport costs on land. Cost of transport by walking Amblyrhynchus (0.37-0.88 ml O2/[g·km]) is similar to Conolophus and to other lizards and quadruped mammals. Marine iguanas (Tb = 25 C) swam at velocities up to 1.7 km/h with reduced metabolic rates relative to walking iguanas. Metabolic cost of swimming at 1.0 km/h was found to be one-fourth the cost of walking at the same speed for adult iguanas. Passive reduction of body temperature while in water, coupled with increased speeds attainable by swimming, function to reduce both time and energy spent foraging. Foraging costs are generously estimated to approximate less than 10% of Amblyrhynchuss 24 h energy budget. Hypothetical foraging on land would cost Amblyrhynchus approximately 31% of its 24 h energy budget.

Muscle fiber-type variation in lizards (Squamata) and phylogenetic reconstruction of hypothesized ancestral states

SUMMARY Previously, we found that phrynosomatid lizards, a diverse group common in the southwestern USA, vary markedly in fiber-type composition of the iliofibularis (a hindlimb muscle important in locomotion). Phrynosomatidae comprises three subclades: the closely related sand and horned lizards, and their relatives the Sceloporus group. The variation in muscle fiber-type composition for 11 phrynosomatid species is attributable mainly to differences between the sand- and horned-lizard subclades. Here, we expand the phrynosomatid database with three additional species and compare these results with data collected for 10 outgroup (distantly related) species. Our goal was to determine if the patterns found in Phrynosomatidae hold across a broader phylogenetic range of the extant lizards and to elucidate the evolution of muscle fiber-type composition and related traits. To allow for meaningful comparisons, data were collected from species that are primarily terrestrial and relatively small in size (3.5–65 g body mass). Results indicate that the fiber-type variation observed within the Phrynosomatidae almost spans the range of variation observed in our sample of 24 species from eight families. However, one species of Acanthodactylus (Lacertidae) had a consistent region of large tonic fibers (that did not stain darkly for either succinic dehydrogenase or myosin ATPase activity), a fiber-type only occasionally seen in the other 23 species examined. Many species have a large proportion of either fast-twitch glycolytic (FG; e.g. sand lizards and Aspidoscelis) or fast-twitch oxidative-glycolytic (FOG) fibers (e.g. horned lizards), with the slow-oxidative proportion occupying only 1–17% of the iliofibularis. Importantly, the negative relationship between FG and FOG composition observed in Phrynosomatidae appears to be a characteristic of lizards in general, and could lead to functional trade-offs in aspects of locomotor performance, as has previously been reported for Lacertidae. Reconstruction of ancestral trait values by use of phylogenetically based statistical methods indicates especially large changes in fiber-type composition during the evolution of horned lizards.

Anaerobic Metabolism in a Lizard (Anolis bonairensis) under Natural Conditions

Lactate contents of Anolis bonairensis (Sauria: Iguanidae) were measured to determine the extent of anaerobic metabolism under a variety of laboratory and field conditions. Groups of lizards in the laboratory which were resting quietly or active for 3 min contained an average of 0.55 and 1.45 mg lactate/g body mass, respectively. Anoles sampled in the field at four different times of day had a mean lactate content of 0.75 mg lactate/g, a value significantly greater than that of resting animals in the laboratory. Individual lizards in each field group exceeded lactate contents of 1.0 mg/g at all times of the day. Lactate accumulation was proportional to intensity of territorial defense in a separate series of territorial intrusion experiments. This anole commonly undertakes bouts of anaerobic metabolism under natural field conditions, and its behavioral repertoire is considerably extended by this anaerobic ability.

Activity Metabolism in the Lizard Sceloporus occidentalis

Standard levels of oxygen consumption and oxygen consumption and lactate production during and after burst activity were measured in the iguanid lizard Sceloporus occidentalis. The activity capacity of this animal is restricted; it sustains vigorous movement for only 1-2 min. The contribution of aerobic metabolism to that activity is strongly thermally dependent. Maximal levels of oxygen consumption are achieved during activity at 30-40 C. At lower temperatures, significant lags occur in oxygen uptake, which appear to result from restricted ventilation. The maximum aerobic increase above resting levels occurs at 35 C, preferred body temperature of this species. Repayment of the initial stages of oxygen debt is also most rapid at 35 C. Lactic acid concentration reaches high levels during activity, and its formation is greatest at 30 C. Anaerobic metabolism represents 62%-82% of the energy utilized during burst activity, accounting for nearly all of the carbohydrate catabolized. The combination of energy utilization in both aerobic and anaerobic modes gives Sceloporus its highest activity capacity at 30-35 C, the range of body temperatures normally experienced diurnally by this species throughout the year.

Maximal Sprint Speeds and Muscle Fiber Composition of Wild and Laboratory House Mice

We compared males from four groups of house mice (Mus domesticus), all bred and raised under common conditions in the laboratory: randombred Hsd:ICR; a wild population from Wisconsin; hybrids from lab dams; hybrids from wild dams. Wild mice were much faster sprinters (maximal forced sprint speeds over 1.0 m ranged from 2.38 to 3.34 m/s) than were lab mice (range = 0.89-1.68 m/s). Hybrids exhibited intermediate speeds (range = 1.54-2.70 m/s) and body masses, indicating largely additive inheritance. Type-specific mean muscle fiber cross-sectional areas of the gastrocnemius muscle did not differ significantly among groups. Percentage cross-sectional areas occupied by each of the three identified fiber types also did not differ significantly among groups, nor did they covary with body mass. For their body mass, however, lab mice had smaller gastrocnemius muscles than did wild and hybrid mice, which had muscles of similar size. Although we cannot rule out the possibility that smaller gastrocnemius muscles or slight differences in fiber composition account for the lower sprint speeds of the lab mice, we suggest that differences in unmeasured physiological, behavioral or motivational factors are probably the primary cause. This interpretation is supported by a lack of correlation between individual differences in sprint speed and either relative gastrocnemius muscle mass or muscle fiber type composition.

Pulmonary oxygen transport during activity in lizards

Oxygen consumption (MO2), effective alveolar ventilation (Veff), arterial and alveolar PO2 (PaO2, PAO2) and the alveolar-arterial PO2 difference [(A--a)PO2] were determined in the lizards Varanus exanthematicus and Iguana iguana at rest and during treadmill exercise at 35 degrees C. In both species, Veff increased more rapidly than MO2 giving rise to an increased PAO2. In contrast, PaO2 remained unchanged through the highest levels of MO2 attained. As a result, the (A--a)PO2 increased with increasing MO2. We suggest that the observed increase in (A--a)PO2 may be due to a rather low pulmonary oxygen diffusing capacity (DLO2) and limited capacity to increase DLO2 during exercise. Arterial desaturation was prevented by a compensatory hyperventilation, thus enhancing the gradient for alveolar-capillary gas exchange. These results indicate that both lizard species increase pulmonary oxygen transport sufficiently so that it is not a limiting factor to aerobic scope under the conditions of this study.

EPOC and the energetics of brief locomotor activity in Mus domesticus

Excess post-exercise oxygen consumption (EPOC) is normally not considered in determinations of the metabolic cost of activity. This approach overlooks an important energetic cost that an animal incurs as a result of activity. To examine the importance of EPOC, we determined how the energetic cost of locomotion was affected by activity of short duration and high intensity. Mice were run at maximum speed on a treadmill while enclosed in an open-flow respirometry system. After sprinting for 5, 15, 30, or 60 sec, each mouse was allowed to recover while remaining enclosed in the respirometry chamber. Exercise oxygen consumption (EOC), the volume of oxygen consumed during the exercise, increased linearly with sprint duration. EPOC was determined as the volume of oxygen consumed after exercise ended until rest was reached. EPOC volumes were found to be constant following 5-60 sec of activity and accounted for > or = 90% of the total metabolic cost. The average EPOC volume of all treatments was 0.76 +/- 0.456 ml O2.gm-1. The net cost of activity (Cact), which considers both EOC and EPOC, decreased as sprint duration increased and varied between 500 ml O2.g-1.km-1 for 5 sec to 30 ml O2.g-1.km-1 for 60 sec of activity. The values for Cact were 15 to 250 times higher than traditional estimates of locomotor costs. From these data, it can be concluded that (1) EPOC is not affected by short exercise durations; (2) EPOC is an important energetic consideration when exercise durations are short; and (3) the metabolic costs of brief, vigorous locomotion may be much higher than previously estimated.

Preferred Body Temperature, Aerobic Scope, and Activity Capacity in the Monitor Lizard, Varanus salvator

Preferred body temperature (PBT), resting and maximal oxygen consumption and carbon dioxide production (V̇o2, V̇co2), and activity capacity as determined by treadmill running were measured in the common water monitor, Varanus salvator. Varanus salvator regulates body temperature at 35–36 C in a thermal gradient with a precision of ±1 C. Resting V̇o2 at PBT = 0.144 ml O₂·g⁻¹·h⁻¹; maximal V̇o2 = 1.10 ml O₂·g⁻¹·h⁻¹. Maximum sustainable treadmill speed equaled 0.5 km/h, speeds in excess of 0.5 km/h elicited R values (R = V̇co2/V̇o2) of 1.4-1.6 and resulted in rapid fatigue. The activity capacity of V. salvator is less than anticipated for a varanid lizard of its size and V̇o2 max The maximal V̇o2 of V. salvator is expressed in a manner independent of differences in body mass and compared to other lizards at 35 C. The data suggest that the aerobic capacities of varanid lizards are quite variable, and that some lizards of other families may, in fact, be more aerobic than some varanid species.