Biomedical subjects

G E Duncan

Publications and source records attributed to G E Duncan.

At least 37 records · Page 2Linked to original sources

PubMed1998

Induction of Fos-like proteins and ultrasonic vocalizations during ethanol withdrawal: further evidence for withdrawal-induced anxiety.

The ethanol withdrawal syndrome includes anxiety as a prominent symptom. Because the extent that specific regions of brain are critical to the generation of this emotional state is unknown, Fos-like immunoreactivity (Fos-LI) was used to associate specific regions of the rat brain with the anxiety component of the ethanol withdrawal syndrome exacerbated by an air puff challenge in rats. Chronic ethanol liquid diet was administered intragastrically for 4 days or by having the rats consume the diet for 14 days. During withdrawal from either treatment protocol, Fos-LI was induced most prominently in forebrain areas, although the midbrain and hindbrain were also represented. Included in these Fos-LI positive regions were many cortical regions, septum, accumbens, claustrum, amygdala, paraventricular nucleus of the thalamus and hypothalamus, hippocampus, locus coeruleus, and central gray. Fos-LI expression differed mostly in intensity between the two treatment and withdrawal protocols, with the gastric protocol producing the greatest Fos-LI induction in most brain regions. The threshold for air puff-induced ultrasonic vocalizations was decreased, and the number of vocalizations was increased and the period of vocalization was extended. These behavioral data indicate that aversively motivated responding in rats during ethanol withdrawal can be readily quantified with the ultrasonic vocalizations test without precipitating convulsive activity. Furthermore, a comparison of the effects of the air puff challenge versus withdrawal on Fos-LI indicated that the behavioral state induced in these two situations share functional neuroanatomical features. Some regions--such as the accumbens core, medial septum, subregions of the amygdala, hippocampus, substantia nigra, and cerebellum--exhibited little Fos-LI during withdrawal and also did not exhibit strong increases after the addition of the air puff challenge. However, other regions-such as the cerebral cortex (medial prefrontal, frontal, cingulate and ventrolateral orbital, claustrum, and tenia tecta), hypothalamus, and locus ceoruleus- exhibited Fos-LI at levels higher than that seen after either the ethanol withdrawal or puff challenge alone. These overlapping patterns of Fos-LI in specific regions of the brain, activated by both ethanol withdrawal and an anxiety provoking behavioral challenge, suggest that specific neuroanatomical sites in brain are associated with the symptom of anxiety observed during the "ethanol withdrawal syndrome."

Alcohol Withdrawal Delirium↗

PubMed1998

Sensitivity to ethanol across development in rats: comparison to [3H]zolpidem binding.

Previous research has suggested that rats tested at 28 to 30 days of age show a marked subsensitivity to the sedative effects of ethanol. In the present study, rats of different ages were tested for aerial righting following acute ethanol (3 g/kg) treatment. These results were compared with the effects of the atypical benzodiazepine zolpidem (3 and 5 mg/kg) and pentobarbital (10 and 15 mg/kg). Animals tested at 25, 28, or 35 days of age were significantly less impaired by ethanol than preweanling rats (age 20 days) or older rats (age 65 to 75 days), whereas animals tested at 25 or 28 days of age were less impaired by the higher dose of zolpidem. With pentobarbital, the most distinct age-related trend was greater impairment in 20-day-old rats. Because ethanol may be active at the same type I GABA(A) receptor site selectively labeled by [3H]zolpidem, levels of [3H]zolpidem binding were determined for rats of different ages. Although some brain regions showed progressive increases in binding of [3H]zolpidem across development, other regions demonstrated increased binding from day 12 or 17 to day 20, then a plateau of binding levels across days 20, 25, and 28, with further increases occurring by day 36 or day 60. This pattern was observed in the cingulate cortex, medial septal nucleus, globus pallidus, inferior colliculus, red nucleus, and cerebellum. Overall, the results indicate that the period of subsensitivity to the sedative effects of ethanol is coincident with a change in the developmental pattern of GABA(A) receptor sites targeted by [3H]zolpidem.

Age Factors↗

PubMed1997

Changes in plasma tryptophan/branched chain amino acid ratio in responses to training volume variation.

The major symptoms of overtraining including decreased exercise performance, altered mood states, and depleted muscle glycogen stores closely resemble the effects of brain serotonin, the level of which is dependent on the plasma ratio of tryptophan to branched-chain amino acids (BCAA). To examine the relation between plasma amino acids and overtraining, ten highly-trained endurance runners underwent two weeks of base training (normal training) before increasing their training volume by 40% for two weeks to achieve a state of short-term overtraining (or overreaching). The overtraining period was followed by two weeks of recovery in which training volume was reduced by 41% of the base training. For the whole group, no significant changes were observed in running economy and maximum oxygen uptake. There were no changes in resting heart rate, blood pressure, resting metabolic rate, and serum cortisol level in response to the changes in training volume. The runners experienced a significant increase (p < 0.05) in fatigue score for the profile of mood states when the training volume was increased. The elevated fatigue score returned to baseline when the training volume was reduced. Plasma free or total tryptophan, BCAA, and the tryptophan/BCAA ratio were not significantly altered throughout the course of this study. We concluded that proposed physiological markers of overtraining, including plasma tryptophan and BCAA levels, were unchanged despite a 40% increase in training volume.

Adult↗

PubMed1997

Applicability of VO2max criteria: discontinuous versus continuous protocols.

This study compared the classic discontinuous Taylor et al. (1955) protocol to a continuous version of the same protocol to evaluate maximal physiological responses, and the quantitative values and incidence of achievement of the various maximal oxygen uptake (VO2max) criteria in 10 males (24.1 +/- 2.5 yr). Criteria were a plateau in VO2 (change < 2.1 ml.kg-1.min-1), HR = age adjusted maximal, PER > or = 1.15, and lactate > 8 mmol.l-1. Values for VO2max (56.8 +/- 4.7 vs 55.8 +/- 4.2 ml.kg-1.min-1), ventilation (150.7 +/- 16 vs 149.5 +/- 17.5 l.min-1 BTPS), and HR (186.3 +/- 7.7 beats.min-1 vs 191.7 +/- 6.7 beats.min-1) were similar (P < 0.05) between the discontinuous protocol (DT) and the continuous protocol (CT), respectively. Values for RER (1.28 +/- 0.05 vs 1.22 +/- 0.05) and lactate (14.3 +/- 2.7 vs 11.9 +/- 2.7 mmol.l-1) were greater (P < 0.05) on the DT than the CT. Criteria achievement were the following: 40% (CT) and 10% (DT) for HR; 50% (CT) and 60% (DT) for a VO2 plateau; and, 90% (CT) and 100% (DT) for RER and lactate. It is concluded that a VO2 plateau is not a prerequisite for defining VO2max and is of limited use as the primary objective criterion for evaluating the quality of a graded exercise test. Therefore, the achievement of secondary objective criteria, specifically RER and lactate in combination, increases the likelihood that the highest VO2 value achieved is VO2max.

Adult↗

PubMed1997

Energy cost of stair climbing and descending on the college alumnus questionnaire.

In calculating the physical activity index (PAI) on the college alumnus questionnaire, it is assumed that 8 kcal are expended for every 20 steps climbed. This value is equal to an energy cost of 0.40 kcal.step-1. Since it is assumed that subjects climb and descend an equal number of stairs, the total value reflects the energy cost of stepping up (estimated at 0.30 kcal.step-1) and stepping down (estimated at 0.10 kcal.step-1). However, these values appear to be based on theoretical calculations rather than empirical observation. The purpose of this study was to quantify the energy cost of stair climbing and stair descending by measuring oxygen uptake. Twenty subjects performed continuous stair-climbing and stair-descending on an escalator at a stepping rate of 70 step.min-1. Heart rate was monitored by telemetry, and oxygen uptake was measured by the Douglas bag technique from 5 to 7 min. Results showed that the gross energy cost of stair climbing is 8.6 METs, and that of stair descending is 2.9 METs. Thus, for a 70-kg person the gross caloric costs of ascending stairs (0.15 kcal.step-1) and descending stairs (0.05 kcal.step-1) are one-half of the values previously assumed. In conclusion, the algorithm for calculating PAI on the college alumnus questionnaire should be modified to reflect a total cost of 0.20 kcal for going up and down one step. Even more precise estimates can be obtained by adjusting for body weight (going up and down one flight of stairs requires 1.63 MET.min).

Adult↗

PubMed1997

Blood lactate and perceived exertion relative to ventilatory threshold: boys versus men.

The purpose of this study was to examine blood lactate (BLa) levels and ratings of perceived exertion (RPE) in nine boys (10.5 +/- 0.7 yr) and nine men (25.3 +/- 2.0 yr) during exercise relative to ventilatory threshold (VT). VT and VO2max were determined during a graded exercise test on a cycle ergometer. On three additional days each subject exercised for 10 min at either 80, 100, or 120% of the VO2 at VT. Capillary BLa levels and RPE were assessed at minutes 5 and 10 of each trial. VO2max averaged 47.7 +/- 5.4 and 50.2 +/- 6.2 mL x g(-1) x min(-1) in the boys and men, respectively (P > 0.05). VT expressed as %VO2max was 67.2 +/- 3.5% in the boys and 67.3 +/- 4.9% in the men (P > 0.05). BLa levels ranged from 2.0 +/- 0.7 to 4.7 +/- 0.9 mmol x L(-1) in the boys and from 2.6 +/- 0.5 to 8.2 +/- 2.1 mmol x L(-1) in the men across the three intensities. Corresponding RPE values ranged from 11.2 +/- 1.8 to 16.2 +/- 2.2 in the boys and from 10.2 +/- 1.2 to 15.8 +/- 1.7 in the men. A group x time x intensity interaction (P < 0.05) indicated that BLa in the men increased more so across time and intensity. There were no significant group difference or interactions involving RPE during exercise. Setting exercise intensity relative to VT did not abolish child-adult differences with respect to submaximal BLa levels. Despite maintaining lower BLa levels, RPE values were similar between boys and men.

Adult↗

PubMed1996

Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety.

Immunohistochemical staining for Fos-like immunoreactivity (Fos-LI) was used to map functional activation in discrete brain regions of rats processed in three empirical models of anxiety: foot shock avoidance responding in a shuttle box, the elevated plus maze, and an air puff-induced ultrasonic vocalization test. The avoidance test and elevated plus maze induced prominent Fos-LI in select brain regions, including the medial prefrontal, cingulate, and ventrolateral orbital cortices, taenia tecta, nucleus accumbens, paraventricular nucleus of the hypothalamus, medial nucleus of the amygdala and lateral septum. Air puff stimuli that produced ultrasonic vocalizations induced Fos-LI to a more limited extent compared to the plus maze and avoidance test, with only the medial prefrontal cortex, medial nucleus of the amygdala, and lateral septum being significantly affected by air-puff. Even though the sensory stimuli and environmental conditions associated with the three anxiety models were markedly different, specific common forebrain regions were affected, i.e. the medial prefrontal cortex, medial amygdala, and lateral septum. It is hypothesized that these regions are components of a circuit in the rat brain related to anxiety or distress. To determine the potential relationship between generalized arousal and the observed induction of Fos-LI in the anxiety models, rats were tested in a non-aversive situation involving marked behavioral activation. Accordingly, after vigorous bar pressing behavior for reinforcement with sweetened condensed milk, induction of Fos-LI was minimal and comparable to that in unhandled control rats. These latter data indicate that the distinctive neuroanatomical patterns of Fos-LI observed in the paradigms related to anxiety were not simply due to generalized behavioral activation. In summary, select common brain regions were identified that express Fos-LI in empirical models of anxiety. These data provide a functional framework to explore neuroanatomical sites of action of psychotherapeutic drugs that influence behavioral responses in these tasks.

Animals↗

PubMed1996

Physiological correlates of 3-kilometer running performance in male children.

The purpose of this study was to examine the influence of body fatness, aerobic and anaerobic ability on 3-km running performance in 19 physically active boys (mean +/- SD, age = 10.4 +/- 0.9 yrs). The sum of six skinfolds, VO2 at 8.04 and 9.65 km.hr-1, and VO2max were measured in the laboratory. Run time for 3 km was assessed twice on separate days on a 200-meter indoor track. Prior to each run, every child performed two 55-meter sprints and two vertical jumps. Mean +/- SD values for the sum of skinfolds, %VO2max at each running speed, VO2max and 3-km run time were: 33.9 +/- 14.9 mm; 70.6 +/- 6.6% and 81.0 +/- 7.9%; 54.6 +/- 5.0 ml.kg-1.min-1; 16.41 +/- 2.58 min, respectively. Significant (p < 0.05) correlations were observed between the following variables and run time: sum of skinfolds (r = 0.72); vertical jump (r = 0.67); sprint time (r = 0.59); VO2max (r = 0.61); and, %VO2max at each treadmill speed (r = 0.79 and r = 0.75, respectively). Stepwise multiple regression analysis indicated that the combination of the %VO2max at 8.04 km.hr-1 and vertical jump accounted for 83% (adjusted R2) of the variance in running time (SEE = 1.06 min, p < 0.05). This study suggests that 3-km run time in physically active boys is influenced by aerobic and anaerobic indices as well as body fatness, supporting the notion that children, compared to adults, are not metabolic specialists.

Body Constitution↗

PubMed1996

Accuracy of five electronic pedometers for measuring distance walked.

This is a three-part study that examined the accuracy of five brands of electronic pedometers (Freestyle Pacer, Eddie Bauer, L.L. Bean, Yamax, and Accusplit) under a variety of different conditions. In Part I, 20 subjects walked a 4.88-km sidewalk course while wearing two devices of the same brand (on the left and right side of the body) for each of five different trials. There were significant differences among pedometers (P < 0.05), with the Yamax, Pacer, and Accusplit approximating the actual distance more closely than the other models. The Yamax pedometers showed close agreement, but the left and right Pacer pedometers differed significantly (P = 0.0003) and the Accusplit displayed a similar trend (P = 0.0657). In Part II, the effects of walking surface on pedometer accuracy were examined. Ten of the original subjects completed an additional five trials around a 400-m rubberized outdoor track. The devices showed similar values for sidewalk and track surfaces. In Part III, the effects of walking speed on pedometer accuracy were examined. Ten different subjects walked on a treadmill at various speeds (54, 67, 80, 94, and 107 m.min-1). Pedometers that displayed both distance and number of steps were examined. The Yamax was more accurate than the Pacer and Eddie Bauer at slow-to-moderate speeds (P < 0.05), though no significant differences were seen at the fastest speed. While there are variations among brands in terms of accuracy, electronic pedometers may prove useful in recording walking activities in free-living populations.

Adolescent↗

PubMed1996

Beta-adrenergic receptor subtypes in human pineal gland.

The secretion of melatonin by the pineal has been promoted as a direct monitor of adrenergic function in depressive illness. However, discrepant findings have been reported, possibly reflecting a complex adrenergic regulation of pineal output. In order to clarify the anatomical localization and relative density of beta-adrenergic receptors and their subtypes in human pineal, quantitative autoradiographic analysis was conducted of beta-adrenergic receptors in postmortem specimens using the high affinity radioligand 125I-pindolol. Dense specific binding was found throughout the gland. beta 1 -adrenergic receptors were more numerous, but beta 2-receptors were present in an overlapping anatomical distribution with beta 1-receptors.

Adrenergic beta-Antagonists↗

PubMed1996

Functional classification of antidepressants based on antagonism of swim stress-induced fos-like immunoreactivity.

Autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake and immunocytochemical assessment of Fos-like immunoreactivity (Fos-LI) were used to assess swim stress-induced changes in metabolic activity in brain and to define the effect of chronic treatment with antidepressants from different pharmacological classes. Saline-treated rats processed in the forced swim test exhibited marked increases in Fos-LI in limbic cortical regions, lateral septum, medial amygdala and paraventricular nucleus of the hypothalamus (PVN). Uptake of 2-DG was increased by swim stress in some of the same brain regions where Fos-LI was induced, with the notable exception of a lack of a change in the PVN. Rats received injections for 3 wk with imipramine, desipramine, fluoxetine, nisoxetine, tranylcypromine or mianserin before being processed in the forced swim test. Chronic treatment with imipramine and desipramine alone induced Fos-LI in the central nucleus of the amygdala and the dorsolateral bed nucleus of the stria terminalis. After tranylcypromine treatment, Fos-LI was induced in many brain regions including limbic cortex, amygdala and paraventricular nucleus of the hypothalamus. None of the other antidepressants induced Fos-LI in any brain region examined. Chronic administration of imipramine, desipramine and nisoxetine antagonized the swim induced expression of Fos-LI in the PVN and in limbic cortical regions, including the medial prefrontal ventrolateral orbital and cingulate cortices. Chronic treatment with fluoxetine, tranylcypromine and mianserin did not alter swim stress-induced Fos-LI in any brain region. Thus, only antidepressant drugs that affect norepinephrine uptake (i.e., imipramine, desipramine and nisoxetine) antagonized swim stress-induced Fos-LI. In contrast to the action of chronic imipramine on Fos-LI induced by swim, chronic administration of imipramine did not antagonize the stress-induced changes in 2-DG uptake in limbic cortical regions. Acute administration of propranolol, which blocks beta-adrenergic receptors, reduced the number of cells staining for Fos-LI in limbic cortical regions, resembling the effects produced by chronic imipramine, desipramine and nisoxetine. In the PVN, neither propranolol nor prazosin (an alpha 1 antagonist) blocked the swim-induced Fos-LI, suggesting that swim-induced Fos-LI in the PVN is not under control of beta- or alpha 1-adrenergic receptors. These latter results imply that adaptation of noradrenergic receptors by chronic imipramine may not be related to the antagonism of stress-induced Fos-LI. The clear functional differences of the various antidepressant agents on swim stress-induced Fos-LI after chronic administration provide a functional classification of antidepressant drug action not previously identified.

Animals↗

PubMed1995

Metabolic and functional mapping of the neural network subserving inferior collicular seizure generalization.

The sensory-motor portion of the inferior collicular cortex is capable of seizure genesis that is characterized initially by coincident wild running behaviors and localized electrographic afterdischarge. With repeated stimulations, this seizure activity spreads into the forebrain, producing generalized tonic-clonic or myoclonic seizure activity. In order to characterize the neural network subserving this caudal-rostral seizure generalization, three mapping techniques were used: 2-deoxyglucose (2-DG) utilization, c-fos expression and local anesthetic microinjection. Kindled seizure generalization from the inferior collicular cortex produced a global increase in 2-DG accumulation, while relative 2-DG increases were found in the inferior collicular cortex, dorsal lateral lemniscus, dorsal central gray, peripeduncular nucleus, medial geniculate nucleus, substantia nigra, entopeduncular nucleus, ventroposterior and centromedian thalamus and tenia tectum, as well as the perirhinal, somatosensory and frontal cortices. Kindled seizure generalization also increased c-fos-like immunoreactivity (FLI) in the inferior collicular cortex, cuneiform nucleus, dorsal lateral nucleus of the lateral lemniscus, peripeduncular nucleus, caudal central gray, dentate gyrus of the hippocampus, rhinal fissure area of the perirhinal cortex and the frontal cortex. Microinjections of procaine into the amygdala, perirhinal cortex, entopeduncular nucleus, substantia nigra, peripeduncular nucleus, dorsal central gray, and pontine reticular nucleus all prevented generalized seizure behaviors, but had no effect on the wild running seizures. Conversely, procaine microinjection into the area of the cuneiform nucleus/pedunculopontine tegmental nucleus prevented the wild running seizure but did not block the generalized seizure activity. Neither wild running, nor generalized seizures were altered following procaine microinjections into the anterior thalamus, sub-thalamus, lateral hypothalamus, hippocampus or deep superior colliculus. Thus, specific forebrain sites form a widespread neural network that mediates the generalization of seizure activity from the inferior collicular cortex into the forebrain.

Animals↗

PubMed1995

Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the alpha 1, beta 2 and gamma 2 subunits of GABAA receptors in rat brain.

Localization of the messenger RNAs that encode the alpha 1, beta 2 and gamma 2 subunits of GABAA showed a distinct topographic pattern in rat brain which corresponded with [3H]zolpidem binding in most brain regions. The close topographic correspondence between the specific receptor subunits examined and the distribution of [3H]zolpidem binding sites provides support for the hypothesis that this benzodiazepine type 1 selective ligand binds to a GABAA receptor that consists of alpha 1, beta 2 and gamma 2 subunits in the rat brain. Brain regions with relatively high densities of alpha 1, beta 2 and gamma 2 subunits of GABAA and [3H]zolpidem binding included olfactory bulb, medial septum, ventral pallidum, diagonal band, inferior colliculus, substantia nigra pars reticulata and specific layers of the cortex. Two areas with low [3H]zolpidem binding and a virtual absence of these GABAA receptor subunit messenger RNAs were the lateral septum and the striatum. In contrast to the discrete pattern observed for alpha 1 and beta 2 subunit messenger RNAs, the gamma 2 subunit messenger RNA was distributed more diffusely in brain. Only the hippocampus, layer 2 of the piriform cortex and the cerebellum showed a strong concentration of the gamma 2 subunit messenger RNA. It was determined with a polymerase chain reaction assay that both long and short variants of the gamma 2 subunit messenger RNAs were present within several of the brain sites selected for examination. Sites with high densities of [3H]zolpidem binding sites had a greater relative abundance of the gamma 2 long splice variant, compared to the gamma 2 short variant. There were some regions that expressed high levels of alpha 1, beta 2 and gamma 2S subunit messenger RNAs but low [3H]zolpidem binding, suggesting that gamma 2 splice variant expression may modulate high-affinity [3H]zolpidem binding. To determine relationships between in vitro [3H]zolpidem binding and functional sensitivity in vivo, interactions between zolpidem and GABA were assessed in brain regions that contained high and low densities of [3H]zolpidem binding sites. In the medial septum, a brain region with a high concentration of [3H]zolpidem binding sites, iontophoretic application of zolpidem enhanced the inhibitory effect of GABA responses on 70% of the neurons examined. In the lateral septum, which contains very low densities of [3H]zolpidem binding sites, neurons were not sensitive to zolpidem enhancement of GABA-induced inhibition. These electrophysiological results demonstrate a correspondence between the regional distribution of [3H]zolpidem binding in vitro and functional sensitivity to the drug in vivo.

Animals↗

PubMed1995

Regional differences in the effects of chronic ethanol administration on [3H]zolpidem binding in rat brain.

A strong association has been observed between [3H]zolpidem binding and the presence of gamma-aminobutyric acid (GABAA) receptor mRNA for alpha 1-, beta 2-, and gamma 2-subunits in specific brain regions. This correlates with observed sensitivity of individual neurons to zolpidem and ethanol in these same regions. Previous studies using homogenate binding approaches showed small alterations in [3H]zolpidem binding levels after chronic ethanol exposure. This study was undertaken to ascertain if there is regional specificity of the effects of chronic ethanol administration on [3H]zolpidem binding levels. Chronic ethanol administration induced small, but significant alterations in [3H]zolpidem (5 nM) binding in the inferior colliculus, substantia nigra, and the medial septum. [3H]Zolpidem binding was increased in the inferior colliculus and substantia nigra, and decreased in the medial septum. No significant differences in [3H]zolpidem binding were noted in any other brain area analyzed, including the cortex and cerebellum. These findings show that chronic ethanol administration has small effects on [3H]zolpidem binding, although they occur in a site-specific and bidirectional manner. Moreover, there is no correlation between changes in [3H]zolpidem binding and alterations in GABAA receptor subunit expression.

Alcoholism↗

PubMed1995

Effect of zolpidem on gamma-aminobutyric acid (GABA)-induced inhibition predicts the interaction of ethanol with GABA on individual neurons in several rat brain regions.

Previous investigations have suggested a relationship between zolpidem binding within specific brain regions and the ability of ethanol or zolpidem to enhance gamma-aminobutyric acid (GABA)-induced inhibition. The purpose of the present study was to extend our electrophysiological analysis to additional brain sites with high levels of zolpidem binding. In the brain regions chosen, red nucleus and globus pallidus, GABA-induced inhibition was shown to be enhanced by either ethanol or zolpidem on some, but not all, neurons. These findings led to the hypothesis that the effect of zolpidem on GABA-induced inhibition would predict the action of ethanol on responses to GABA for that neuron. When zolpidem and ethanol were applied individually to the same neurons in the red nucleus and globus pallidus, those neurons sensitive to zolpidem enhancement of GABA also were sensitive to ethanol. Conversely, if zolpidem did not enhance responses to GABA, ethanol did not enhance responses to GABA at these brain sites. A similar relationship between the abilities of zolpidem and ethanol to enhance GABA-induced inhibition was obtained in 90% of the neurons studied in the medial septum/diagonal band and ventral pallidum. These studies provide further support for the contention that the zolpidem-sensitive GABAA-benzodiazepine isoreceptor also responds to ethanol. Finally, the expression of GABAA subunit mRNAs was analyzed by polymerase chain reaction from micropunches of several brain regions that contain zolpidem binding sites and exhibit sensitivity to ethanol. Polymerase chain reaction analysis proved more sensitive than in situ hybridization in the detection of receptor subunit mRNAs. Several subunits (alpha 1, alpha 2, alpha 3, beta 2, beta 3 and gamma 2) were common to all brain regions in which ethanol and zolpidem enhanced GABA responses. GABAA receptor alpha 4/5, alpha 6, beta 1, gamma 1, gamma 3 and delta subunits were not consistently expressed in association with the presence of zolpidem binding. These data are consistent with the view that one native GABAA receptor to which zolpidem binds, and on which ethanol acts, contains the GABAA receptor subunits alpha 1, beta 2 and gamma 2; however, the present investigation did not preclude the possibility that other subunit combinations can contribute to ethanol and zolpidem enhancement of responses to GABA.

Animals↗

PubMed1994

Brain activity patterns in flying, echolocating bats (Pteronotus parnellii): assessment by high resolution autoradiographic imaging with [3H]2-deoxyglucose.

Brain activity patterns during echolocation and flight were assessed in mustached bats (Pteronotus parnellii parnellii). Bats were injected intraperitoneally with [3H]2-deoxyglucose and restrained in a foam holder or allowed to fly for 20 min. Under resting conditions, low levels of [3H]2-deoxyglucose uptake were observed throughout the forebrain but relatively high uptake was found in brainstem auditory and vestibular centers. In flying, echolocating bats, marked increases in regional [3H]2-deoxyglucose uptake were apparent. All structures of the classical ascending auditory pathway were intensely labeled in autoradiograms. Other brain regions that exhibited high [3H]2-deoxyglucose uptake in flying bats included the cingulate cortex, stratum lacunosum-moleculare of the hippocampus, thalamus, caudate-putamen, superior colliculus, pontine reticular formation, nucleus ambiguus, parts of the midbrain central gray, and cerebellum. In the cerebellum, the most prominent increase in [3H]2-deoxyglucose uptake was found in discrete patches of the granule cell layer. The results provide the first overview of brain activity patterns during echolocation and flight in bats. In addition, uptake of [14C]fluorodeoxyglucose was used to compare brain activity patterns in flying bats to bats that were imaging their environment via biosonar while hanging in a wire cage. The echolocating-not-flying bats emitted 6931 +/- 1226 pulses in 20 min compared to 8972 +/- 1273 pulses in 20 min for flying bats. The uptake of the metabolic marker was significantly more in the flying bats compared to the emitting-not-flying bats in the medial geniculate, superior colliculus, auditory cortex, cingulate cortex and thalamus. In the nucleus ambiguus, cochlear nucleus, and inferior colliculus, uptake was similar for the flying and emitting-not-flying bats. These results suggest that the high metabolic activity observed in forebrain auditory regions of flying bats is related in part to neural processes that involve sensory motor integration during flight and not simply the perception of acoustic information.

Animals↗

PubMed1994

Ontogeny of D1A and D2 dopamine receptor subtypes in rat brain using in situ hybridization and receptor binding.

The prenatal and postnatal ontogeny of D1A and D2 dopamine receptors was assessed by in situ hybridization of messenger RNAs encoding the receptors and by radioligand binding autoradiography. On gestational day 14, signals for D1A and D2 dopamine receptor messages were observed in selected regions in ventricular and subventricular zones which contain dividing neuroblasts, and in intermediate zones that contain maturing and migrating neurons. Specifically, D1A and D2 dopamine receptor message was observed in the developing caudate-putamen, olfactory tubercle, and frontal, cingulate, parietal and insular cortices. Additionally, D1A dopamine receptor messenger RNA was found in the developing epithalamus, thalamus, hypothalamus, pons, spinal cord and neural retina; D2 dopamine receptor messenger RNA was also observed in the mesencephalic dopaminergic nuclear complex. Gene expression of D1A and D2 dopamine receptor subtypes in specific cells as they differentiate precedes dopamine innervation and implies that receptor expression is an intrinsic property of these neurons. The early expression of dopamine receptor messenger RNA suggests a regulatory role for these receptors in brain development. While the signal for both messages increased in the intermediate zones on gestational day 16, it decreased in the ventricular and subventricular zones, and was no longer apparent in these zones by gestational day 18. By gestational day 18, abundant D1A or D2 dopamine receptor messenger RNA was observed in cell groups similar in location to those observed in the adult brain. On gestational day 18, D1A dopamine receptor message was noted in the neural retina, anterior olfactory nucleus, the insular, prefrontal, frontal, cingulate, parietal and retrosplenial cortices, the olfactory tubercle, caudate-putamen, lateral habenula, dorsolateral geniculate nucleus, ventrolateral and mediolateral thalamic nuclei, and the suprachiasmatic and ventromedial nuclei of the hypothalamus. D2 dopamine receptor message was observed on gestational day 18 in the insular, prefrontal, frontal and cingulate cortices, the olfactory tubercle, caudate-putamen, ventral tegmental area, substantia nigra, and the intermediate lobe of the pituitary. At birth, expression of messenger RNA for both dopamine receptor subtypes in the striatum approximated that seen in mature rats. In contrast, D1A and D2 receptor binding, measured with [3H]SCH-23390 and [3H]raclopride, respectively, was low at birth and progressively increased to reach adult levels between days 14 and 21. The in situ hybridization data showing early prenatal expression of messenger RNA for the D1A and D2 dopamine receptors are consistent with the hypothesis that these receptors have a regulatory role in neuronal development.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1994

The effect of exercise on serum and salivary cortisol in male children.

The purpose of this study was to examine serum and salivary cortisol responses to cycling exercise in male children, 10.6 +/- 0.2 yr (mean +/- SE). Each child performed a graded exercise test on a cycle ergometer to determine VO2max. On a separate day, a 30-min bout of exercise at 70% of VO2max was performed. Blood, obtained from a venous catheter, and saliva samples were collected at rest, at 15 and 30 min of exercise, and 15 min post-exercise. The mean serum cortisol level at 15 min (7.94 +/- 1.43 micrograms.dl-1) and 30 min (8.72 +/- 1.77 micrograms.dl-1) of exercise and at 15 min post-exercise (8.21 +/- 1.59 micrograms.dl-1) were significantly greater than rest (5.54 +/- 0.86 micrograms.dl-1). The increase in salivary cortisol levels over time approached (P = 0.08), but did not reach significance. However, effect size analyses indicated that the increase in salivary cortisol at 30 min of exercise (0.64) and 15 min post-exercise (0.62) was similar to the change in serum cortisol at these same two time points (0.72 and 0.66, respectively). Serum and salivary cortisol were correlated (P < 0.05) at 15 min of exercise (r = 0.77), 30 min of exercise (r = 0.90), and 15 min post-exercise (r = 0.84), but not at rest (r = 0.46). In conclusion, 30 min of submaximal exercise at 70% of VO2max significantly increased serum cortisol level; and salivary and serum cortisol are correlated during and after exercise.

Analysis of Variance↗