Short communication: Analytical method and amount of preservative added to milk samples may alter milk urea nitrogen measurements.

Milk urea N (MUN) is used by dairy nutritionists and producers to monitor dietary protein intake and is indicative of N utilization in lactating dairy cows. Two experiments were conducted to explore discrepancies in MUN results provided by 3 milk processing laboratories using different methods. An additional experiment was conducted to evaluate the effect of 2-bromo-2-nitropropane-1, 3-diol (bronopol) on MUN analysis. In experiment 1, 10 replicates of bulk tank milk samples, collected from the Pennsylvania State University's Dairy Center over 5 consecutive days, were sent to 3 milk processing laboratories in Pennsylvania. Average MUN differed between laboratory A (14.9 ± 0.40 mg/dL; analyzed on MilkoScan 4000; Foss, Hillerød, Denmark), laboratory B (6.5 ± 0.17 mg/dL; MilkoScan FT + 6000), and laboratory C (7.4 ± 0.36 mg/dL; MilkoScan 6000). In experiment 2, milk samples were spiked with urea at 0 (7.3 to 15.0 mg/dL, depending on the laboratory analyzing the samples), 17.2, 34.2, and 51.5 mg/dL of milk. Two 35-mL samples from each urea level were sent to the 3 laboratories used in experiment 1. Average analyzed MUN was greater than predicted (calculated for each laboratory based on the control; 0 mg of added urea): for laboratory A (23.2 vs. 21.0 mg/dL), laboratory B (18.0 vs. 13.3 mg/dL), and laboratory C (20.6 vs. 15.2 mg/dL). In experiment 3, replicated milk samples were preserved with 0 to 1.35 mg of bronopol/mL of milk and submitted to one milk processing laboratory that analyzed MUN using 2 different methods. Milk samples with increasing amounts of bronopol ranged in MUN concentration from 7.7 to 11.9 mg/dL and from 9.0 to 9.3 mg/dL when analyzed on MilkoScan 4000 or CL 10 (EuroChem, Moscow, Russia), respectively. In conclusion, measured MUN concentrations varied due to analytical procedure used by milk processing laboratories and were affected by the amount of bronopol used to preserve milk sample, when milk was analyzed using a mid-infrared analyzer. Thus, it is important to maintain consistency in milk sample preservation and analysis to ensure precision of MUN results.

An inhibitor persistently decreased enteric methane emission from dairy cows with no negative effect on milk production.

A quarter of all anthropogenic methane emissions in the United States are from enteric fermentation, primarily from ruminant livestock. This study was undertaken to test the effect of a methane inhibitor, 3-nitrooxypropanol (3NOP), on enteric methane emission in lactating Holstein cows. An experiment was conducted using 48 cows in a randomized block design with a 2-wk covariate period and a 12-wk data collection period. Feed intake, milk production, and fiber digestibility were not affected by the inhibitor. Milk protein and lactose yields were increased by 3NOP. Rumen methane emission was linearly decreased by 3NOP, averaging about 30% lower than the control. Methane emission per unit of feed dry matter intake or per unit of energy-corrected milk were also about 30% less for the 3NOP-treated cows. On average, the body weight gain of 3NOP-treated cows was 80% greater than control cows during the 12-wk experiment. The experiment demonstrated that the methane inhibitor 3NOP, applied at 40 to 80 mg/kg feed dry matter, decreased methane emissions from high-producing dairy cows by 30% and increased body weight gain without negatively affecting feed intake or milk production and composition. The inhibitory effect persisted over 12 wk of treatment, thus offering an effective methane mitigation practice for the livestock industries.

Mucous contribution to gut nutrient content in American gizzard shad Dorosoma cepedianum.

This study developed and applied an approach to calculate the proportion of fish gut content composed of mucus secreted by the oropharyngeal cavity and gut. The amount of nitrogen in the contents of the foregut (oesophagus and gizzard) and the epibranchial organs of suspension-feeding American gizzard shad Dorosoma cepedianum was significantly higher than the nitrogen in the homogeneous food source. Using data collected from suspension-feeding experiments and the nitrogen content of D. cepedianum mucus, a series of equations illustrated that mucus constituted c. 10% of D. cepedianum foregut content and 12% of epibranchial organ content by dry mass. Future quantification of fish feeding selectivity and absorption efficiency can use this approach to take into account the contribution of fish mucus to the nutrients in the gut contents. This study supports the conclusion that suspension-feeding D. cepedianum in a heterogeneous environment selectively ingest nutrient-rich particles, even when gut nutrient content is adjusted to take into account the contribution of mucus.

Fibromuscular dysplasia recurrence after kidney transplantation: case report.

We report the extremely rare recurrence of intimal fibroplasia, a rare form of fibromuscular dysplasia, in a kidney recipient at 6 months after transplantation from a living-related donor. The patient was successfully treated and maintains good kidney function, however, the case raises the question of whether kidneys with fibromuscular dysplasia should be included in the expanded criteria for kidney transplantation.

The influence of uridine diphosphate glucuronosyl transferase 1A promoter polymorphisms, beta-globin gene haplotype, co-inherited alpha-thalassemia trait and Hb F on steady-state serum bilirubin levels in sickle cell anemia.

PURPOSE: Homozygosity for the (AT)7 allele of uridine diphosphate glucuronosyl transferase 1A (UGT1A1) gene polymorphism is associated with increased bilirubin levels in sickle cell anemia (SCA). In the present study, in addition to UGT1A1 promoter genotype, serum bilirubin level was related to other genetic modifiers -beta(S)-globin gene haplotype, Hb F, co-inherited alpha-thal trait, age and gender. METHODS: The patients were randomly selected from the sickle cell clinic, Medical College of Georgia. UGT1A1 promoter polymorphisms were determined using automated sequencing. Other investigations were with standard techniques. RESULTS: There were 67 SCA patients (41 males and 26 females), aged 2-44 yr (mean of 20.6 +/- 10.7). Ten (14.9%) patients were homozygous for the (AT)6 UGT1A1 allele, 35 (52.2%) were heterozygous for (AT)6 and (AT)7 alleles while 22 (32.8%) were homozygous for (AT)7. Serum bilirubin was significantly higher in the homozygous (AT)7 group (3.7 +/- 1.5, 3.8 +/- 2.3 and 5.6 +/- 2.4 mg/dL, respectively). It was also significantly higher in males than females and in patients aged >10 yr. There was a significant negative linear correlation (r = -0.304, P = 0.016) of serum bilirubin with Hb F. The beta-globin haplotype and co-existing alpha-thal trait did not have any significant influence on serum bilirubin levels. Patients on hydroxyurea were older, had lower Hb F, but higher mean serum bilirubin. The latter also was signifcantly higher among those with UGT1A1 (AT)7 homozygosity. CONCLUSIONS: Apart from UGT1A1 (AT)7 homozygosity, Hb F, age and gender are the other factors that significantly influence serum bilirubin level in SCA.

Postmortem molecular diagnosis of sickle beta thalassaemia.

This report describes a case in which the diagnosis of sickle cell disease (SCD) was established after death. The diagnosis of sickle cell syndrome was made in a 68 year old black patient who was found to have sickled red blood cells in many organs at necropsy although the disease had not been diagnosed during her lifetime. DNA was isolated from a peripheral blood smear obtained on the day of the patient's death. The beta globin gene was polymerase chain reaction amplified and sequenced, revealing that the patient had S-beta(+) thalassaemia. This study shows that blood smears are a suitable source for retrospective DNA analysis studies. This case illustrates that relatively "mild" forms of SCD can be overlooked, despite symptomatology suggestive of a sickle syndrome, and demonstrates the feasibility of the postmortem molecular diagnosis of haemoglobinopathies in such cases.

Influence of fibrinogen and haematocrit on erythrocyte sedimentation kinetics.

This study investigates the influence of haematocrit, fibrinogen concentration and fibrinogen availability (amount of fibrinogen per red blood cell) on erythrocyte sedimentation. The Westergren technique was applied to blood samples from 36 subjects and to their blood manipulated to haematocrits of 10, 20, 30 and 40%. Readings were taken every 10 minutes for 300 minutes. Previous studies indicate that erythrocyte sedimentation occurs in three phases. In this study, we show that haematocrit has little influence on either the rate of fall of particles in the first phase (m1) or the duration of the first phase. This is also true for fibrinogen availability and for fibrinogen concentration at low haematocrits. At high haematocrits m1 increases with fibrinogen concentration. The rate of fall of rouleaux during phase 2 (m2) and ESR60 both decrease exponentially with haematocrit and increase linearly with fibrinogen concentration. While m2 is more closely correlated to fibrinogen availability than to fibrinogen concentration or to haematocrit, this is not the case for ESR60. Thus haematocrit, fibrinogen concentration and fibrinogen availability are more important to the velocity of sedimentation in the second phase than to the sedimenting velocity during phase 1 or to the duration of phase 1.

Ventricular fibrillation and defibrillation thresholds in sheep and dogs.

Ventricular defibrillation studies normally use dogs rather than other large species. To investigate the suitability of sheep, which are often cheaper and more readily available, we compared ventricular fibrillation and defibrillation thresholds (VFT, DFT) in sheep and dogs. A total of 12 sheep (31 +/- 5 kg) and six dogs (19 +/- 1 kg) were anesthetised with halothane. Fibrillation was induced via epicardial pacing leads, using a 1 s 50 Hz pulse. Biphasic defibrillation shocks were delivered across epicardial patches. Voltage-response curves for both fibrillation and defibrillation were generated. Logistic regression analysis was used to determine 50 and 90% probability of success for fibrillation induction and defibrillation. VFT was similar in sheep and dogs. DFT at 50% probability of success was significantly higher in sheep (369 +/- 14 V) than in dogs (299 +/- 31 V, P < 0.04) but within each species there was no correlation between heart weight and DFT. After defibrillation sheep took longer to return to sinus rhythm than dogs and electro-mechanical dissociation was observed in sheep, but not in dogs. Thus, sheep may not be an ideal model for ventricular defibrillation research but further studies of the intrinsic differences between sheep and dogs may provide insights into basic mechanisms of defibrillation.

Reducing electrical defibrillation thresholds with glibenclamide in an isolated rabbit heart preparation.

Glibenclamide has been shown to prevent ischemia-induced shortening of action-potential duration (APD) and to prolong effective refractory period (ERP). Glibenclamide also has been shown to prolong APD under normal conditions. The aim of this study was to test the hypothesis that glibenclamide would prolong APD and ERP in the nonischemic heart by blocking adenosine triphosphate-sensitive K+ (K(ATP)) channels in myocardium, thus reducing defibrillation energy requirements. Hearts from 15 adult male New Zealand White rabbits, weight 3.1 +/- 0.1 kg, were perfused with a Krebs-Henseleit solution containing either no drugs (five hearts) or glibenclamide (10 hearts) at six concentrations ranging from 30 nM to 10 microM. Two 140-mm2 Pt-Ir mesh patch electrodes were sutured onto the ventricles. A 3.5/2.5-ms biphasic pulse (impedance, 95 +/- 16 omega) with randomly selected voltages of 20, 30, 50, 70, 90, or 110, defibrillated the heart after 10 s of fibrillation. The APD, ERP, fibrillation threshold (FT), and defibrillation threshold (DFT) were determined from monophasic action potentials, computer-controlled pacing, 50-Hz sinusoidal pacing, and multiple defibrillation shocks, respectively. Defibrillation thresholds were determined from a total of 180 fibrillation and defibrillation sequences, conducted in each preparation, and the results were fitted to a sigmoid dose-response curve by logistic regression analysis. Five repeated observations of APD, ERP, FT, and DFT showed no change over a 5-h period, whereas for DFT, there was a significant increase between first and next four determinations. With glibenclamide (100 and 300 nM, and 1 and 10 microM), a dose-dependent difference (p < 0.05) compared with controls was observed. There was an increase in APD, ERP, and FT and a decrease in DFT at 50% success (V50). The maximal effect for each parameter occurred at 300 nM. Glibenclamide dose-dependently reduced DFT and increased FT in an isolated nonischemic rabbit heart preparation. A probable mechanism is through APD and ERP prolongation by blocking ATP-sensitive K+ channels, suggesting that these channels may be important in modifying the APD and ERP during electrical defibrillation. This might be of particular interest in reducing electrical-defibrillation thresholds, thereby minimizing heart damage.

Dilated duct pattern at mammography.

PURPOSE: To determine the importance of a dilated duct pattern at mammography. MATERIALS AND METHODS: Mammograms obtained in 46 women with histopathologically proved, asymmetrically dilated ducts were retrospectively studied. The laterality and location of the asymmetrically dilated duct, the presence of branching, and associated findings such as microcalcifications, nipple discharge, and interval change were evaluated. RESULTS: Eleven patients (24%) had malignant results (ductal carcinoma in situ or invasive ductal carcinoma). Among these, six (54%) had suspicious microcalcifications. Nonsubareolar location and interval change are significant (P = .04) variables associated with malignancy. CONCLUSION: Mammographic asymmetrically dilated ducts in a nonsubareolar area that are associated with interval change, suspicious microcalcifications, or both warrant biopsy.

Transmembrane potentials during high voltage shocks in ischemic cardiac tissue.

Transmembrane, voltage sensitive fluorescent dye (TMF) recording techniques have shown that high voltage shocks (HVS), typically used in defibrillation, produce either hyper- or depolarization of the transmembrane potential (TMP) when delivered in the refractory period of an action potential (AP) in normal cardiac tissue (NT). Further, HVS produce an extension of the AP, which has been hypothesized as a potential mechanism for electrical defibrillation. We examined whether HVS modify TMP of ischemic tissue (IT) in a similar manner. In seven Langendorff rabbit hearts, recordings of APs were obtained in both NT and IT with TMF using di-4-ANEPPS, and diacetylmonoxime (23 microM) to avoid motion artifacts. Local ischemia was produced by occlusion of the LAD, HVS of either biphasic (5 + 5 ms) or (3 + 2 ms) or monophasic shapes (5 ms) were delivered at varying times (20%-90%) of the paced AP. Intracardiac ECG and TMF recordings of the TMP were each amplified, recorded, and digitized at a frequency of 1 kHz. The paced AP in IT was triangular in shape with no obvious phase 3 plateau, typically seen in NT. There was normally a reduced AP amplitude (expressed as fractional fluorescence) in IT (2.6% +/- 1.79%) compared to 3.8% +/- 0.66% in NT, and shortened AP duration (137 +/- 42 vs 171 +/- 11 ms). One hundred-Volt HVS delivered during the refractory period of paced AP in IT in five rabbits, elicited a depolarization response of the TMP with an amplitude up to three times greater than the paced AP. This is in contrast to NT where the 100-V HVS produced hyperpolarization in four hearts, and only a slight depolarization response in one heart. These results suggest that HVS, typically delivered by a defibrillation shock, modify TMPs in a significantly different manner for ischemic cells, which may influence success in defibrillation.

Erythrocyte sedimentation in columns and the significance of ESR.

Erythrocyte Sedimentation Rate (ESR) is a simple, non-specific clinical test. Most models of erythrocyte sedimentation (ES) are formulated as a sigmoid function but consider the ES process to consist of three distinct phases: single-cell fall; fall of rouleaux and aggregates; cell packing. Recently, a piecewise (three-phase) continuous model has been developed. Our study applies ES data from 29 haematologically normal subjects to this model and re-evaluates the mechanism of ES using the derived model parameters. Using the Westergren technique, ES readings were taken every 10 minutes for 300 minutes. Three subjects remained in the first phase, while 26 displayed three discrete phases. For the 26 subjects, the average rate of fall of the sedimenting particles in the first phase 87 microns/min, while that of the second phase was 176 microns/min. The ratio of these two values suggests an alternative nature of sedimenting particles in the first phase. Further, the average duration of the first phase was 62 minutes, suggesting that, in 50% of subjects, aggregate formation is incomplete when ESR is measured at 60 minutes.

Effects of benzodiazepine receptor inverse agonists and nicotine on behavioral vigilance in senescent rats.

Previous experiments demonstrated that, compared with 6-month-old rats, the performance of 20-month-old rats in a behavioral vigilance task was characterized by an impairment in their ability to detect visual signals, whereas their ability to discriminate between longer signals and nonsignal events was unaffected. The benzodiazepine receptor (BZR) agonist chlordiazepoxide potently and selectively interacted with the effects of age on the relative number of hits. However, negative modulators of GABAergic transmission (Zk 93 426, beta-CCtB, RU 33965) failed to attenuate the effects of age on behavioral vigilance. the present experiment tested the hypothesis that the performance of senescent animals (28 months) is further impaired and thus would allow the demonstration of beneficial effects of BZR inverse agonists or nicotine. However, administration of ZK 93 426 (0.39, 1.56, 6.25 mg/kg), Ru 33965 (0.1, 0.5 mg/kg), or nicotine (0.09, 0.287, 0.689 mg/kg) did not beneficially affect the performance of senescent animals; rather, detrimental effects were found. Considering the beneficial behavioral effects of these compounds in animals with experimentally induced impairments in cholinergic function, the present finding point to limitations of normal aging as a variable in animal experiments on BZR inverse agonist or nicotine-induced attenuation of cognitive impairments that result from cholinergic hypofunction.

Characterization of shock-induced action potential extension during acute regional ischemia in rabbit hearts.

INTRODUCTION: Defibrillation shocks produce extension of the myocardial action potential repolarization time (AP extension) in nonischemic myocardium. AP extension may synchronize repolarization in the heart because the extension increases when shock timing is increased. We tested whether AP extension occurs and whether it increases when shock timing is increased in regionally ischemic isolated perfused rabbit hearts stained with the transmembrane voltage sensitive fluorescent dye, di-4-ANEPPS and given diacetyl monoxime to eliminate motion artifacts. METHODS AND RESULTS: Before and after left anterior descending (LAD) coronary artery occlusion, APs were recorded on the anterior left ventricular epicardium with an epifluorescence measurement system. Hearts were paced with a train of 10 stimuli (S1) and then during the 10th AP were given a defibrillation shock (S2) from epicardial electrodes on either side of the recording region. Before LAD occlusion, duration of the 9th S1-induced AP measured at full repolarization was 171 +/- 11 msec (mean +/- SD). Within 15 minutes after LAD occlusion, the AP duration became shorter (P < 0.05) and more variable (137 +/- 47 msec), and APs with negligible plateaus were observed. Extension of the 10th AP by S2 was significant both before (mean extension of 59 to 65 msec for three S2 waveforms tested) and after LAD occlusion (mean extension of 35 to 41 msec). Unlike the results before LAD occlusion, AP extension after occlusion was independent of absolute shock timing expressed in msec. When timing was expressed as a fraction of individual AP durations, AP extension after occlusion increased with increases in shock timing. CONCLUSIONS: Shocks extend APs during ischemia; however, absolute time dependence of AP extension is not constant among cells that have different AP durations during ischemia. This may influence postshock repolarization synchrony when different AP durations exist in different parts of regionally ischemic hearts.

Dissociation between the attentional effects of infusions of a benzodiazepine receptor agonist and an inverse agonist into the basal forebrain.

The effects of infusions of the benzodiazepine receptor (BZR) full agonist chlordiazepoxide (CDP) or the full inverse agonist beta-CCM into the basal forebrain on behavioral vigilance were tested. Vigilance was measured by using a previously characterized task that requires the animals to discriminate between visual signals of variable length and non-signal events. Measures of performance included hits, misses, correct rejections, false alarms, side bias, and errors of omission. Following the infusion of saline (0.5 microliters/hemisphere), the relative number of hits varied with signal length. In response to shorter signals, the number of hits decreased over time, indicating a vigilance decrement. Infusions of CDP (20, 40 micrograms/hemisphere) initially decreased the relative number of hits in response to shorter signals and, later in the course of the test sessions, to longer signals as well. CDP did not affect the relative number of correct rejections. In contrast, infusions of the inverse agonist beta-CCM (1.5, 3.0 micrograms/hemisphere) did not affect the relative number of hits but decreased the relative number of correct rejections (i.e., increased the number of false alarms). These data suggest that the basal forebrain mediates the attentional effects of BZR ligands. As systemic or intrabasalis administration of BZR agonists and inverse agonists was previously demonstrated to decrease and augment, respectively, activated cortical acetylcholine (ACh) efflux, their effects on behavioral vigilance are hypothesized to be mediated via their effects on cortical ACh.

Effects of nicotinic acetylcholine receptor ligands on behavioral vigilance in rats.

The effects of nicotinic receptor ligands on performance in a task measuring sustained attention, or vigilance, were tested. This task required the animals to discriminate between signal and non-signal events. The sequence of signal (central panel light illumination for 500, 50 or 25 ms) and non-signal presentations was randomized over three blocks of 54 trials each (27 signal trials, 9 per length, and 27 non-signal trials). A left lever press following a signal was counted as a hit, and a right lever press following a non-signal event was counted as a correct rejection. Hits and correct rejections were rewarded, whereas misses and false alarms (defined as incorrect right and left lever presses, respectively) were not. Baseline performance was characterized by a signal length dependent ability of the animals to discriminate between signal and non-signal events. Administration of nicotine (0.19, 0.62, 1.9 mumol) or of two novel nicotinic receptor agonists, ABT-418 and A-82695, did not produce main effects on vigilance performance. Lobeline (1.9, 6.2, 19 mumol), a nicotinic receptor ligand with mixed agonist/antagonist activities, impaired the animals' ability to discriminate between signal and non-signal events. The antagonist mecamylamine (5, 15, 50 mumol) potently impaired performance while increasing the number of errors of omission. The lack of effect of nicotine largely corresponds with the findings from previous studies on the acute effects of nicotine in intact subjects and non-smoking humans. While the detrimental effects of lobeline may have been related to the antagonist effects of this compound, the reasons for the differences between the effects of nicotine and lobeline still remain unsettled. These data support the hypothesis that nicotine receptor mechanisms are maximally activated in intact animals performing this task, and suggest that effects of acute nicotinic agonist treatment would not produce further cognitive benefit for these animals.

Cortical cholinergic deafferentation following the intracortical infusion of 192 IgG-saporin: a quantitative histochemical study.

The immunotoxin 192 IgG-saporin has been hypothesized to selectively lesion cholinergic neurons that bear the low-affinity p75 nerve growth factor (NGF) receptor. To evaluate the usefulness of this toxin in studies intended to determine the functions of cholinergic afferents of cortical areas, relatively small concentrations and volumes of the immunotoxin (0.01-0.05 micrograms/0.5-1.0 microliters) were infused into cortical areas of one hemisphere of rats, while the vehicle was infused into homologous areas of the contralateral hemisphere. The effects of these infusions on the density of cortical acetylcholinesterase (AChE)-positive fibers and of normal fibers (as revealed by a reduced silver stain) were quantified. The infusion of the immunotoxin did not produce local gliosis in excess of the gliosis resulting from the infusion of vehicle. When compared with the frontoparietal cortex of the intact hemisphere, the number of cortical AChE-positive fibers was reduced by 36-39% and the density of the silver-stained fibers was decreased by 20-25%. While the loss of AChE-positive fibers and silver-stained fibers correlated significantly in layers V/VI, a linear regression analysis suggested that the magnitude of the loss of AChE-positive fibers was greater than would be predicted on the basis of the residual density of normal fibers. Thus, the data suggest that infusions of 192 IgG-saporin into the cortex did not result in the loss of non-cholinergic afferents. Intracortical infusions of relatively small concentrations and volumes of 192 IgG-saporin appear to provide a useful approach for the examination of the functions of cholinergic inputs to specific cortical regions.

Interactions between the effects of basal forebrain lesions and chronic treatment with MDL 26,479 on learning and markers of cholinergic transmission.

The effects of ibotenic acid-induced basal forebrain lesions and treatment with the triazole MDL 26,479 on the acquisition of an operant visual conditional discrimination task and on [3H]hemicholinium-3 and [3H]vesamicol binding were examined. Lesioned animals required more training sessions to acquire the stimulus-response rules of this task. They also showed longer response latencies throughout the experiment. The effects of the treatment with MDL 26,479 (5 mg/kg; i.p. 60 min before each training session) interacted with the effects of the lesion, producing a decrease in the number of sessions required to perform above chance-level in lesioned but not in control animals. MDL 26,479 did not seem to produce immediate performance effects but interacted with the learning process. The lesions destroyed the cell bodies in the area of the substantia innominata, basal nucleus of Meynert, and the globus pallidus. The number of frontocortical cholinergic terminals as primarily indicated by hemicholinium-3 binding was reduced in lesioned animals; however, another measure of cholinergic terminals, vesamicol binding, was unchanged. Behavioral performance of animals correlated significantly with hemicholinium binding in the frontal cortex of the right hemisphere. The fact that the lesion delayed but did not block the acquisition of the task may have been a result of compensatory mechanisms in remaining cholinergic terminals as indicated by stable vesamicol binding. These data allow assumptions about the conditions for the demonstration of beneficial behavioral effects of MDL 26,479. They also suggest that the long-term effects of basal forebrain lesions on cortical cholinergic transmission remain unsettled.

Attenuation of muscarinic receptor blockade-induced impairment of spatial delayed alternation performance by the triazole MDL 26,479.

The interactions between the effects of MDL 26,479 (0.1, 0.39, 1.56, 6.25 mg/kg; IP) and the muscarinic antagonist scopolamine (0.03, 0.1 mg/kg; IP) on the performance of rats in a delayed alternation task (retention intervals: 2, 4, 8, 16, 32 s) were examined. Scopolamine dose-dependently reduced the relative number of correct responses and interacted with the effects of the length of retention intervals. MDL 26,479 did not affect correct responding but attenuated the behavioral impairments produced by scopolamine. Although this task did not explicitly exclude the possibility that the animals acquired mediational response strategies, and although the effects of scopolamine appeared to interfere with the execution of these strategies, to a major extent, the attenuative effects of MDL 26,479 were not related to its effects on mediational strategies. Thus, it is concluded that administration of MDL 26,479 mainly resulted in a re-establishment of the animals' ability to memorize and/or to recall the information required to exert correct responses.