10-min Blocks Research Articles

Identification and time dependence of quantitative trait loci for basal locomotor activity in the BXD recombinant inbred series and a B6D2 F2 intercross.

A complimentary two-phase strategy was used to detect and map quantitative trait loci (QTLs) associated with the basal locomotor response to a saline challenge (10 ml/kg). In phase 1, putative QTLs, significant at p < 0.01 or better, were identified by analysis of the strain means for 25 strains of the B x D recombinant inbred series. QTLs were identified on chromosomes 1, 3, 5, 9, 10, 16, and 18. Some of these QTLs were detected across the entire experimental period (0-20 min), while others were associated with specific 5-min blocks. Eighteen hundred C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for the basal locomotor response, and of this group, 500 to 700 individuals, pseudo-randomly selected, were used for a genomewide scan to confirm the RI-generated QTLs and to detect new QTLs. No new QTLs were detected but the QTLs on chromosome 1 were confirmed at p < 10(-5) to p < 10(-9), depending on the time interval. In addition, the QTLs on chromosomes 5 and 9 were confirmed at p < 0.001, providing a combined probability (RI + F2) which exceeds the threshold for a significant association. Two additional phenotypes which showed significant RI strain differences were examined--adaptation and thigmotaxis. Adaptation mapped to the same region of chromosome 9 and thigmotaxis to the same region of chromosome 1 as the distance-traveled QTL. Overall, the data presented here and elsewhere (Flint et al., 1995; Gershenfeld et al., 1997) illustrate that QTLs for basal activity are both robust and reliable.

Effects of amperozide and tiospirone, atypical antipsychotic 5-HT 2 drugs, on food-reinforced behavior in rats

Amperozide (AMPZ) is a 5-HT 2 receptor antagonist that can decrease consumption of ethanol and prevent cocaine conditioning of a place preference. Tiospirone (TSP) is a 5-HT 2 receptor antagonist with affinity for D 2, 5-HT 1a, and 5-HT 7, and sigma receptors, which can decrease consumption of ethanol while increasing food intake. Both drugs were tested for inhibition of food reinforced bar-pressing behavior. Fasted Sprague–Dawley male rats were trained daily on a 15-min FR-5 schedule. After response rates stabilized, each rat in one group received a 60-min pretreatment s.c. with saline, 0.25, 0.75, or 2.5 μmol/kg of AMPZ (injections were twice per week and counterbalanced). Each rat in a second group received a 60-min pretreatment with saline, 0.1, 0.3, or 1.0 μmol/kg of TSP. The dose of 2.5 μmol/kg of AMPZ reduced the number of food reinforcements by 21% from saline. The effect was due to a greater decline in bar pressing during the last 5-min block. TSP, 0.3 and 1.0 μmol/kg, significantly reduced the number of reinforcements by 45 and 94% from saline, respectively. In a study of catalepsy, TSP at 0.3 and 1.0 μmol/kg produced akinesia and catalepsy, respectively. Our results indicate that AMPZ-induced reduction of alcohol intake is not due to a nonspecific effect on reward, but the akinetic effects of TSP masks whether or not it has effects on reward.

Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant.

Transplantation has been shown to improve cardiorespiratory reflex measures of autonomic function. However, there are limited data on how kidney or kidney-pancreas transplantation influence continuous autonomic modulation of heart rate and the clinical utility of 24-hr heart rate variability (HRV) monitoring. Ninety nondiabetic kidney and 30 diabetic kidney-pancreas transplant recipients underwent 24-hr Holter monitoring before and again at 6 and 12 months posttransplantation. Tapes were submitted for determination of HRV including interbeat variability (the proportion of adjacent R-R intervals having a difference <50 msec, the SD of all R-R intervals for the entire recording, and the SD of the averages of R-R intervals calculated over 5-min blocks for the entire recording) which is associated with vagal function, sudden death, and circadian function, respectively. Power spectral analysis quantified total neural, sympathetic, and parasympathetic modulation of the heart in ln(msec2). Nondiabetic kidney recipients showed improvement (P< or =0.05) in the SD of the averages of R-R intervals calculated over 5-min blocks (83.2 vs. 95.7 msec) and the SD of all R-R intervals (94.5 vs. 104.4 msec) by 6 months and all groups showed improvement by 12 months. Kidney-pancreas recipients also showed improved total neural (4.35 vs. 4.64) and sympathetic modulation (2.70 vs. 3.13). Kidney-pancreas recipients had significantly poorer values for each measure (P< or =0.05) at all time points. Cardiac autonomic neuropathy arises in the presence of uremia and diabetes, with severe dysfunction seen when these conditions occur concomitantly. Improvement in cardiac autonomic function follows both kidney and kidney-pancreas transplantation with more pronounced improvement in the circadian measures. Therefore, circadian measures of 24-hr HRV could be used to monitor the restoration of cardiac autonomic function.

Primary nociceptive afferents mediate the blood flow dysfunction in non-glabrous (hairy) skin of type 2 diabetes: a new model for the pathogenesis of microvascular dysfunction.

To test the independent contributions of vascular endothelium, sympathetic activation and inhibition, vessel distensibility, and nociceptor-mediated vasodilation in both glabrous and hairy skin circulations. We measured blood flow using laser Doppler techniques in 10 people with type 2 diabetes and 10 age- and BMI-matched healthy control subjects at the pulp of the index finger (glabrous skin) and the dorsum of the hand (hairy skin). A 5-min ischemic block of the arm was used to test vascular endothelium. Warming of the probe site to 45 degrees C tested neurogenic vasodilation in hairy skin only. Vessel distensibility was tested by gravitational pressure. Basal blood flow and reactive hyperemia did not differ between groups at either skin site. The vasodilative response to local warming (P < 0.01) and limb lowering (P < 0.05) were significantly different between groups in hairy skin but not in glabrous skin in the absence of objective measured neuropathy. Nociceptor-mediated flow correlated significantly with the warm thermal threshold (r = -0.50, P < 0.05). Endothelial-mediated blood flow correlated with systolic blood pressure (r = -0.76, P < 0.01), LDL cholesterol (r = -0.62, P < 0.001), C-peptide (r = 0.65, P < 0.05), and triglycerides (r = 0.47, P < 0.05). These data suggest that neurogenic nociceptor-mediated vasodilation is impaired in subjects with type 2 diabetes when endothelial and sympathetic function are relatively intact. Heat-induced vasodilation may be a specific test of small heat-sensitive C-fiber peripheral neurons and may be an integral part of the metabolic syndrome.

Prepulse Inhibition of the Startle Reflex: Preliminary Study of the Effects of a Low Dose of Alcohol in Humans

The present study was designed to examine the effects of a low dose of alcohol on prepulse inhibition (PPI) of the startle response and self-report measures of affect. Eighteen subjects participated in a counterbalanced repeated-measures design in which they received a beverage with alcohol during one session and a nonalcohol beverage during a different experimental session. The startle response was probed in two separate 10-min blocks immediately after consumption of the alcohol. Although alcohol significantly suppressed the startle response in general, it did not do so to an extent that compromised detection of PPI. The effects of alcohol on PPI were primarily evident in the first block and were dependent on baseline levels of PPI, such that alcohol resulted in a reduction of PPI in subjects who demonstrated low PPI at baseline and an increase in PPI for subjects with high PPI at baseline. Alcohol also significantly increased self-reported stimulation during the first block and increased negative affect during the second block. These findings suggest that baseline PPI may reflect an important individual difference that is predictive of the direction and magnitude of alcohol-induced changes in sensorimotor gating.

A method for the delivery of reinforcement during exercise

The purpose of this study was to develop an automated system for positively or negatively reinforcing subjects while they exercised on an electronically braked bicycle ergometer. The circuitry used to interface the subject’s pedal speed responses with the delivery of auditory reinforcement is presented, as well as a study designed to test the utility of the system. Twenty 18- to 25-year-old male subjects exercised on an electronically braked ergometer at a constant workload of 50 W for three 5-min blocks. During the first 5 min, subjects pedaled at their preferred rate, and during the next two 5-min blocks, they pedaled faster or slower than their baseline pedal speed to turn on a comedy tape for positive reinforcement, or turn off 90 dB of white noise for negative reinforcement. Circuits that interfaced the subject’s pedal response with the delivery of reinforcement are discussed in detail. Both positive and negative reinforcement increased the targeted pedaling rates, with no differences as a function of targeting increased or decreased pedal speed. This system could be used with various reinforcers, such as video and other audio equipment to increase exercise behavior.

Time-Related Changes in Neural Systems Underlying Attention and Arousal During the Performance of an Auditory Vigilance Task

Vigilance behavior, or watch keeping, involves the focusing of attention on the detection of subtle changes in the environment that occur over a long period of time. We investigated the time course of changes in brain activity during the continuous performance of a 60-min auditory vigilance task. The task required the detection of an intensity drop that occurred in 5% of the auditory stimuli. Six 1-min samples of cerebral blood flow (CBF) and electroencephalographic (EEG) activity were obtained at l0-min intervals during the vigilance performance. Changes in CBF were measured by means of positron emission tomography (PET). Performance data (hits, false alarms, reaction time) were analyzed across six 10-min blocks. Eight healthy male volunteers participated in the study. During the 60-min test, the number of correct detections (hits) did not change, but both the reaction time and EEG activity in the theta (4 to 7 Hz) range progressively increased across testing. CBF in several subcortical structures (thalamus, substantia innominata, and putamen) and cortical areas (ventrolateral, dorsolateral, and orbital frontal cortex; parietal cortex; and temporal cortex) decreased as a function of time-on-task; changes in the cortical regions were limited to the right hemisphere. Blood flow also decreased in the temporalis muscles. At the same time, CBF increased in several visual cortical areas including the left and right fusiform gyri. Furthermore, the thalamic blood-flow response co-varied with that in the substantia innominata, the ponto-mesencephalic tegmentum, and the anterior cingulate cortex. The right ventrolateral-frontal blood-flow response covaried with that in the right parietal, orbitofrontal, and dorsolateral frontal cortex. 'Iko main conclusions are drawn from the obtained data. First, we suggest that the observed time-related changes in reaction time, EEG activity, and blood flow in the temporalis muscles are related to changes in the level of arousal (alertness) and that CBF changes in the thalamus-related neural circuitry represent a brain correlate of such changes. Second, we speculate that time-related CBF decreases in cortical regions of the right hemisphere underlie a shift from controlled to automatic attentional processing of the auditory stimuli.

Mesolimbic 7-OH-DPAT affects locomotor activities in rats

This study tested the hypotheses that the dopamine D 3 receptor is both an autoreceptor and a postsynaptic receptor and has an affinity for dopamine at the nanomolar level. The effect of bilateral microinjections of a dopamine D 3-like agonist, 7-OH-DPAT, into the nucleus accumbens and into the ventral tegmental area (VTA) was tested with rats in activity monitors. Horizontal movement, rearing, and stereotypy times in seconds were automatically measured during 12 consecutive 10-min time blocks. Intraaccumbens 7-OH-DPAT (0.0001–10.0 μg/side) resulted in a highly significant dose by time block interactions. The dose of 0.0001 μg/side resulted in the potentiation of horizontal movement time during the time blocks 10–40 min; whereas, 0.001–1.0 μg/side potentiated locomotion during the early blocks following the 10-min interval. However, 10.0 μg/side resulted in a biphasic effect, attenuation followed by potentiation. 7-OH-DPAT (0.0001–1.0μg/ side) potentiated rearing time in the early time blocks and (0.001–10.0μg/side) attenuated stereotypy time during the first 20 min time blocks. On the other hand, intra-VTA 7-OH-DPAT (10.0 μg/side) attenuated horizontal movement time during the first 20-min time blocks and (0.01 and 0.0001 μg/side) potentiated movement time at the 20-min time block. Intraventral tegmental area 7-OH-DPAT had no effects on rearing and stereotypy times. These data support the hypothesis that the D 3 receptor has an affinity for dopamine at the nanomolar level and question the hypothesis that the D 3 receptors are both autoreceptors and postsynaptic receptors.

WITHIN‐SESSION RESPONSE RATES WHEN REINFORCEMENT RATE IS CHANGED WITHIN EACH SESSION

Three pigeons pecked keys and 5 rats pressed levers for food delivered on variable-interval schedules. During baseline conditions, subjects responded on a variable-interval 40-s schedule throughout the session. During experimental conditions, the programmed rate of reinforcement changed every 10 min in the 50-min sessions. When rats served as subjects, Herrnstein's (1970) hyperbolic equation provided a good description of the relation between rate of responding during a 10-min interval and the rate of reinforcement obtained during that interval. Responding, measured over 10-min blocks, was also approximately equally sensitive to changes in the programmed rate of reinforcement at all times in the session. Herrnstein's equation provided a poorer description of the changes in responding when pigeons served as subjects. Differences in experimental experience or differences in the absolute rates at which subjects responded may have contributed to the differences in results for these different species.

Intra-accumbens δ1-opioid agonist, pCl-DPDPE, differentially affects patterns of locomotor activity

The effects of bilateral microinjections of a new potent and highly selective δ-opioid receptor agonist pCl-DPDPE (0.00,0.1,1.0, or 2.5 μg/side) were tested in rats for 60 min in activity monitors. The durations of horizontal movement time, rearing time, and stereotypy time were measured during six consecutive 10-min time blocks. The pCl-DPDPE resulted in short-lived biphasic effects of attenuation followed by potentiation for the three measures. These data in part replicate the behavioral effects of other δ-opioid receptor agonists.

DALDA (H-Tyr-D-Arg-Phe-Lys-NH 2), a potent μ-opioid peptide agonist, affects various patterns of locomotor activities

The central effects of μ-opioid receptor agonist DALDA (ICV 0.00, 0.1, or 1.0 μg) were investigated in rats for 120 min on activity monitors. The durations in seconds of horizontal movement time, rearing time, and stereotypy time were measured during 12 consecutive 10-min time blocks. DALDA (ICV, 0.1 and 1.0 μg) resulted in biphasic effects, inhibition followed by activation for horizontal movement, rearing, and stereotypy times.

Relationship between obesity and the metabolic effects of smoking in women.

The influence of cigarette smoking on resting energy expenditure (REE) in normal-weight and obese smokers was investigated. Participants were 20 normal-weight and 20 obese female smokers assessed over a 2-day period. The results indicated that REE increased in both obese and normal-weight smokers after smoking, but the increase was greater for normal-weight participants. The normal-weight group showed a 9.7%, 5.8%, and a 3.6% increase in REE during the three 10-min blocks constituting the 30-min postsmoking phase. However, the obese group showed a 3.9% and a 0.7% increase in REE and a 0.8% decrease in REE during this postsmoking phase. Between-group comparisons revealed a differential rate of change in REE after smoking, indicating that the obese group's change of REE at every postsmoking time point was on average 70 kcal/day below that of the normal-weight group. The metabolic effect of smoking is reproducible, and the obese smokers reliably show an attenuated effect. However, the reliability of the change is lower for both normal-weight and obese smokers. The results have potential implications for discouraging obese persons from taking up smoking and intervening among those who already smoke.

Biphasic effects of intraaccumbens μ-opioid peptide agonist DAMGO on locomotor activities

The effects of bilateral microinjections of μ-opioid receptor agonist DAMGO (0.00, 0.01, 0.1, or 1.0 μg/side) were tested in rats for 12 min in activity monitors. The horizontal movement, rearing, and stereotypy times in seconds were measured during 12 consecutive 10-min time blocks. DAMGO (0.01, 0.1, and 1.0 μg) resulted in biphasic effects, inhibition followed by activation for each of the three measures. These data replicate the behavioral effects of ICV DAMGO except that the duration of the behavioral effects were longer with Acb injections.

Semi-automatic Analysis of Electroencephalogram in Sleep Apnea Syndromes

The present study was undertaken to validate a system of condensed display of the sleep EEG spectral analysis with a view to simplifying sleep studies in patients affected by sleep apnea syndromes (SAS). All subjects underwent polysomnography on two consecutive nights using a Respisomnograph. The 8-h EEG, electro-oculogram, and electromyogram were digitalized. A fast Fourier transform was done and successive spectrums were computed resulting in one spectrum for each 20-s period. Then the EEG spectrum was plotted as a Lofard color diagram. To validate this system we compared a visual analysis of EEG recordings by a trained neurophysiologist with 10-s epochs and a visual analysis of the Lofard diagram by a practitioner with no previous understanding in EEG after only 2 h of instruction. The 8-h recording was divided into 10-min blocks. Each block was staged in function of the amplitude and prevailing frequency of EEG as indicated by the color (wakefulness, light slow wave sleep, deep slow wave sleep, rapid eye movement sleep). The stage of each block was compared with the predominant stage found in this block by the neurophysiologist. Eight normal adults and 24 patients suffering from SAS were recruited. When all the blocks of all patients were pooled (1,438 blocks), agreement was total in 81 percent, partial in 11 percent, and discordant in 8 percent. This system of spectral analysis representation allows a fast evaluation of quality of sleep and of EEG.

Behavioral effects of opioid peptide agonists DAMGO, DPDPE, and DAKLI on locomotor activities

The effects of the μ-selective agonist DAMGO (ICV doses of 0.00, 0.01, 0.1, or 1.0 μg), the δ-selective agonist DPDPE (ICV doses of 0.00, 0.1, 1.0, or 10.0 μg), and the κ-selective agonist DAKLI (ICV doses of 0.00, 0.01, 0.1, or 1.0 μg) were tested in rats for 60 min in an activity monitor. The durations in seconds of linear locomotor time, rearing time, stereotypy time, and margin time (thigmotaxis) were measured during six 10-min time blocks. DAMGO (0.1 and 1.0 μg) resulted in biphasic effects, inhibition followed by hyperactivity for linear locomotor, rearing, and stereotypy times, and an inhibition of thigmataxis. DPDPE (10.0 μg) was associated with monophasic potentiation of linear locomotor activity and mixed effects in stereotypy times. DAKLI did not effect horizontal, rearing, or margin times; only stereotypy times resulted of in mixed effects of DAKLI. THe differentail behavioral profiles were discussed in reference to the three opioid receptor subtypes.

Biphasic effects of dopamine agonist N-0434 on locomotor behaviors in rats

The effects of a dopamine agonist, (±)-2-( N-penylethyl- N-propyl)amino-5-hydroxytetralin (N-0434) (SC doses of 0.00, 0.01, 0.1 and 1.0 mg/kg) were tested in rats for 120 min in an activity monitor. The durations in seconds of horizontal locomotor time, rearing time, stereotypy time, and margin time (thigmotaxis) were measured during 12 10-min time blocks. N-0434 (0.1 and 1.0 mg/kg) resulted in biphasic effects (initial inhibition followed by potentiation) of linear locomotor time and an attenuation of thigmotaxis. The 0.1- and 1.0-mg/kg doses initially suppressed rearing time but had mixed potentiation effects. The 0.01- to 1.0-mg/kg doses suppressed stereotypy time. The differential behavioral profiles were discussed in reference to the functions of dopamine receptors.

Real‐time continuous‐flow spin trapping of hydroxyl free radical in the ischemic and post‐ischemic myocardium

Real-time monitoring of spin-trapped oxygen-derived free radicals released by the isolated ischemic and reperfused rat heart has been achieved by ESR analysis of the coronary effluents using continuous flow detection and high-speed acquisition techniques. Two nitrone spin traps 5,5-dimethyl pyrroline 1-oxide (Me2PnO) and 3,3,5,5-tetramethyl pyrroline 1-oxide (MePnO) have been separately perfused at a concentration of 40 mM during a sequence of 50 min of low-flow ischemia (1 ml/min) followed by 30 min of global ischemia and subsequent reperfusion at the control flow rate (14 ml/min). ESR spectra were sequentially obtained in 5-min or 30-s blocks during low-flow ischemia and reperfusion, respectively. 1. The results show the formation of OH. free radicals in the ischemic and reperfused heart, as demonstrated by the observation of Me2PnO-OH (aN = aH = 14.9 G; g = 2.0053) and Me4PnO-OH (aN = 15.2 G, aH = 16.8 G; g = 2.0055) spin adducts. There is no evidence of significant biological carbon-centered or peroxyl free radicals spin-adduct formation in the coronary effluents or in lipid extracts analyzed after reflow. 2. The OH. generation began 15-20 min after the onset of ischemia and was moderate, peaking at 30-40 min. During reperfusion, an intense formation of OH. spin adducts was observed, with a maximum at 30-60 s and a further gradual decrease over the following 2 min. 3. Cumulative integrated values of the amount of spin adducts released during the ischemic period show a Me2PnO-OH level fourfold greater than that of Me4PnO-OH. It was 2.5 times greater during reflow, reflecting slower kinetics with the more stable Me4PnO. 4. The original ESR detection technique developed in this study allows accurate real-time quantitative monitoring of the oxygen-derived free radicals generated during myocardial injury. It might provide a quick and reliable new means for assessing the efficacy of free-radical inhibitors.

Predictable and unpredictable shock stimulates gastric contractility and causes mucosal injury in rats.

The effects of tailshock on gastric contractility and lesions were investigated in rats exposed to 100 1-mA tailshocks while confined inside plastic tubes. A light preceded each shock in one group and was randomly presented with respect to shock in the other. Following the session, animals were given 3 hr of rest before being sacrificed. Contractility of the corpus of the stomach was measured by means of chronically implanted extraluminal force transducers. Contractility was measured in 10-min blocks and analyzed by computer. Lesions were quantified by inspection; quantitative histology was performed on corpus and antrum sections. Signaled (n = 13) and unsignaled (n = 17) shock stimulated high-amplitude gastric contractions in fasted rats, which continued for 2 hr after the shock session. Cumulative contractile activity (1.5-hr shock plus 2-hr rest) in shocked animals was twice that in restrained and unrestrained control animals (n = 19, p less than .05), and contractile activity had a 30%-40% greater average amplitude than after a meal. Compared with unrestrained controls, shocked rats had visibly more mucosal injury (2.2 +/- 0.5 mm2 vs. 0.1 +/- 0 mm2). Larger cumulative contractile activity was associated with a larger area of erosions (r = .36, p less than .05). Frequency and duration of contractions did not distinguish between shocked and unshocked groups. We conclude that in rats, signaled and unsignaled tailshock stimulates persistent, high-amplitude gastric contractions and is associated with injury of the mucosa of the stomach.

Ethanol effects on female aggression vary with opponent size and time within session

Female rats displayed different patterns of attack to large and small male intruders into their home cages, as a function of ethanol dose levels. In confrontations with small male intruders, female attack increased significantly at 0.3 g/kg ethanol, declining to saline levels with higher doses (0.6 and 1.2 g/kg). Attack toward large intruders was (nonsignificantly) higher at 0.3 g/kg ethanol, and declined to significantly lower than saline levels with the higher ethanol doses. The attack increases seen with low ethanol doses came in the initial 5-min block of the 30 min test session, and did not persist. These findings suggest that low ethanol doses may especially increase overt aggression in situations in which the tendency to attack is only moderately inhibited by factors such as opponent size or the potential danger of retaliatory attack.

Performance of C57BL/6J, DBA/2J, and B6D2F1 mice in a free-operant avoidance task

Male mice (Mus musculus) 12–16 weeks of age from the C57BL/6J and DBA/2J inbred strains and B6D2F1 hybrids were trained at one of two shock levels (.5 or 2.0 mA) in a wheel-turn avoidance task during one 60-min session. Following two 10-min blocks during which no shock was given, a free-operant avoidance program was activated that required the animal to turn a wheel .5 revolution at least once every 10 sec in order to avoid a 1-sec footshock. The program was terminated when the mouse reached an acquisition criterion, which was 5 min of successful shock avoidance, or when it completed the 60-min session without reaching criterion. Strain differences in learning were marked and consistent at both shock levels. Most C57BL/6J mice reached criterion, and most DBA/2J mice failed. The performance of B6D2F1 mice matched that of the C57BL/6J strain.