Phase response curves to ambient temperature pulses in rats

The effect of pulses of warm ambient temperature on the phase of activity onset in Long-Evans hooded rats, Rattus norvegicus, free-running in constant light was examined. In two experiments, rats were exposed to pulses reaching a maximum of 34 degrees C or 32 degrees C. Phase response curves were obtained with advances occurring mainly in the subjective day, and delays mainly, but not entirely, in the subjective night. Significant negative correlations between rhythm period and phase-shifts were found. There were no consistent relationships between changes in activity levels due to the temperature pulses and phase-shifts. Cycles of higher and lower ambient temperature may entrain circadian activity rhythms in mammals by daily advance or delay phase-shifts.     

Effects of preoptic, lateral hypothalamic, or dopamine-depleting lesions on behavioral thermoregulation in rats exposed to the cold.

Results of a study with male albino Sprague-Dawley rats indicate that Ss which received medial preoptic/anterior hypothalamic lesions showed impaired physiological thermoregulation in the cold but continued to barpress to activate a heat lamp. After lateral hypothalamic lesions or 6-hydroxydopamine-induced destruction of central dopaminergic neurons, physiological mechansims for body temperature maintenance were unaffected, but performance of the operant task was impaired. In contrast to this difference, Ss from each of the 3 groups constructed nests from tissue paper that were similar in size to one another. These nests generally were much smaller than those of control Ss. The present findings, together with previous observations of behavioral thermoregulation in rats with comparable lesions, are interpreted in terms of the reinforcement obtained by each behavior and the deficits in detecting those reinforcements that may result from each type of brain damage. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral thermoregulation, core temperature, and motor activity: Simultaneous quantitative assessment in rats after dopamine and prostaglandin E1.

Determined the dose-response autonomic and behavioral thermoregulatory effects and the motor effects of dopamine (DA) and prostaglandin E1 (PGE1) injected into the lateral cerebral ventricles of male Sprague-Dawley rats. The present study was conducted with a computer-controlled thermocline that permitted freely moving Ss to select preferred ambient temperatures (7-39°C). All Ss were studied with the thermocline gradient both on and off to control for nonspecific effects. Results show that PGE1 (0, .1, .2, .5, 1.0 μg) produced a dose-related increase in core temperature and produced a dose-related selection of warmer ambient temperatures. DA (0, 50, 100, 200, 400 μg) produced a dose-related hypothermia and cold-seeking behavior. Without the gradient, DA-injected Ss did not become as hypothermic as in the gradient-on condition. When the gradient was available, Ss showed a significant rebound increase in core temperature 50-80 min after DA, which did not occur when the gradient was off. Overall, DA induced increases in motor activity, but, during the 1st 10 min after injection while the gradient was on, Ss made stable selections of cool ambient temperatures and showed reduced activity. Conversely, the behavioral effect of PGE1 did not facilitate the autonomically mediated heat gain. Findings emphasize the necessity of creating behavioral options for animals to fully evaluate drug effects on thermoregulation. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thermoregulation in newborn lambs: influence of feeding and ambient temperature on brown adipose tissue

We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of brown adipose tissue (BAT) in newborn lambs maintained at a warm (30 degrees C) ambient temperature. This study further examines the effect of ambient temperature on BAT and thermoregulation by investigating the response to feeding 50 ml of water. Immediately after vaginal birth, lambs were placed in either a warm (30 degrees C) or cool (15 degrees C) environment a ambient temperature and measurements of colonic temperature and heat production were recorded for 6 h. Lambs were fed 50 ml of water when 5 h old. The level of guanosine 5'-diphosphate (GDP) binding was higher, but adrenaline content lower in BAT sampled from lambs maintained at 15 degrees C compared with those at 30 degrees C. Feeding was associated with an increase in colonic temperature and plasma concentrations of glucose and non-esterified fatty acids in lambs maintained at 15 degrees C only. In this group plasma concentrations of adrenaline and dopamine declined after feeding, but noradrenaline concentrations were not influenced by feeding in either group of lambs. O2 consumption and CO2 production were higher in lambs maintained at 15 degrees C but were not influenced by ambient temperature or feeding. It is concluded that feeding a small volume of water can influence thermoregulation by a mechanism that is dependent on the ambient temperature at which the lamb is maintained.     

Changes of blood pressure responsiveness in rats exposed in utero and perinatally to a high-salt environment

We tested the hypothesis that the pressor responses to angiotensin II could be influenced by an early salt exposure. Twenty-five adult female rats were pseudorandomly divided in two groups. Twelve animals underwent a partial ligature of their abdominal aorta (PAL). Once polydipsia and sodium appetite developed, these rats were mated. The other group (13 rats) was sham-operated (Sham) and mated. Throughout pregnancy and lactation, water and 2.7% NaCl solution intakes differed between the two groups of mother rats. PAL offspring (PAL-O; n = 14), and Sham-operated offspring (Sh-O; n = 10), were maintained on a solid diet containing 1% NaCl, tap water and a 2.7% NaCl solution. At 90 days of age, pressor responsiveness to intravenous angiotensin II (50, 100 and 200 ng) was assessed in anesthetized rats. The pressor responses to 50 and 200 ng angiotensin II were significantly greater in PAL-O rats than in Sh-O rats. These results support the hypothesis of a modulation of cardiovascular responsiveness or its underlying mechanisms by an early high salt environment.     

Day-night variations of behavioral and autonomic thermoregulatory responses to lipopolysaccharide in rats

This study investigated the day-night differences in behavioral and autonomic thermoregulatory responses to bacterial lipopolysaccharide (LPS) in rats. Male rats were housed individually in cages with a 12: 12 h light dark cycle at an ambient temperature of 24 degrees C. The rats were placed in a box with a temperature gradient and intraperitoneally injected with LPS (10 micrograms/kg). The preferred ambient temperature (Tpr) was estimated by the location of the rats in the box, and intraperitoneal temperature (Tb) was measured by a biotelemetry system. Measurements were taken during the light and dark phases of the day. LPS produced fever in both phases. The magnitude of rise in Tb did not differ between the two periods. In the dark phase, Tpr significantly increased during the development of fever and decreased during the defervescence, while it did not change throughout the febrile course during the light phase. In a separate experiment, rats were loosely restrained and placed in a direct calorimeter. Their colonic temperature (Tcol), evaporative and nonevaporative heat loss and heat production were measured before and after intraperitoneal injections of LPS (10 micrograms/kg). Measurements were taken during the light and dark phases of the day. LPS induced fever in both phases. The magnitude of change in T col, heat loss, and heat production due to LPS did not differ between the two periods. These results suggest that the fertile response of rats to intraperitoneal LPS is not affected by the time of day. However, it seems that during LPS-induced fever, thermoregulatory behavior is not fully activated during the light phase of the day.     

Effects on pubertal growth and reproduction in rats exposed to lead perinatally or continuously throughout development

The purpose of this study was to examine the effects of different exercise intensities with the anaerobic threshold (AT) as the standard on electroencephalograph (EEG) and heart rate variability (HRV). Eleven healthy males, with a mean age of 22 (SD 1.48) years, performed submaximal exercise to determine their ATs, and underwent four experimental conditions including rest (rest), 20% less than the AT level (-20), the AT level (AT), and 20% more than the AT level (+20) for about 20 minutes. EEG and electrocardiogram (ECG) were taken for 15 minutes before and after each experimental condition, respectively. The EEG signals were recorded from Cz, Pz, O1 and O2 (10-20 system). HRV was determined by the R-R interval method of ECG. Spectral analysis was applied to the EEG and the HRV from just before (pre) and after (post) each experimental condition for 5 minutes using the maximum entropy method (MEM). Post/pre ratios were calculated, after the power spectral density (PSD) and percentage of total power (power time percent: Time%) of delta (0.5-4 Hz), theta (4-8 Hz), alpha 1 (8-11 Hz), alpha 2 (11-14 Hz), beta 1 (14-20 Hz), beta 2 (20-30 Hz), total waves in EEG and PSD as to low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) areas, and the LF/HF(L/H) ratio in HRV were analyzed. In the exercise condition, total PSD in the EEG was enhanced and PSD of HF in HRV was significantly declined, as compared to those in the resting condition. Alpha PSDs of occipital sites were higher in -20 than those in AT and +20 conditions. The increase in L/H in AT and +20 demonstrated the changes in the balance of the autonomic nervous system, compared with that in -20. A significant increase in heart rate was observed in +20, although other indicators did not show differences in AT and +20 conditions. No alternations were noted in the gradient of exponential PSD in the above four experimental conditions, that is at rest, -20, AT and +20. These results suggest that the exercise intensity 20% less than one's AT level does not put a great strain on his or her body in health-promoting.     

Ventilatory response to asphyxia in conscious rats: effect of ambient and body temperatures

In many mammals the ventilatory response to hypoxia depends on ambient temperature (Ta), largely because of the hypometabolic effects of hypoxia below thermoneutrality. We questioned whether the ventilatory response to asphyxia also depends upon Ta, and the role played by metabolism and body temperature (Tb). Oxygen consumption (VO2) and pulmonary ventilation (VE) were measured in conscious rats at Ta = 27 degrees C (warm) and 11 degrees C (cold), breathing air or two levels of asphyxic gases, moderate (10% O2-4% CO2), or severe (10% O2-8% CO2), for approximately 30 min each. In the cold, the pattern of the VE response to moderate asphyxia was qualitatively similar to that seen in hypoxia alone, i.e the attained VE/VO2 was similar in warm and cold conditions, with, in the latter, a major drop in VO2 and little or no hyperpnea. During severe asphyxia, however, the VE/VO2 attained in the cold was less than in the warm, and it was accompanied by a large drop in Tb (approximately 6 degrees C). Blood gases confirmed the lower asphyxic hyperventilation in the cold. By maintaining Tb at 38 degrees C with an implanted abdominal heat exchanger, the VE/VO2 levels attained during asphyxia were the same between cold and warm conditions. We conclude that (a) the VE response to asphyxia is Ta-dependent, largely because of the hypometabolic effect of the hypoxic component in the cold, (b) during moderate asphyxia the hypercapnic component is qualitatively unimportant, and (c) with severe asphyxia the hypercapnia becomes an important contributor to the Ta-sensitivity by aggravating the decrease in Tb in the cold and lowering VE sensitivity.     

Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption, and chronic dosing

In two experiments it was found that the hyperthermia which follows MDMA ("Ecstasy") results from an interaction of direct pharmacological effect of the drug and the prevailing environmental conditions in which it is administered. In Experiment 1, rats given fixed doses of either 2.5, 5.0 or 7.5 mg/kg MDMA or saline were injected on different days at ambient temperatures (Ta's) of 11, 24, and 30 degrees C. At each Ta drinking water was freely available following dosing on one session and temporarily unavailable on a second. The hyperthermic and hyperkinetic responses were monitored using remote biotelemetry. Experiment 2 used a between-subject design in which each group of rats received a standard 7.5 mg/kg dose of MDMA administered at only one of the three levels of Ta(24 degrees C) and at only one level of the water-availability factor. Dosing in some groups was continued for a further 13 days to test for tolerance or sensitization effects. Ambient temperature significantly affected the magnitude of the hyperthermia but not the hyperkinesis. Water deprivation during the drugged period significantly augmented the hyperthermia, but only in the high Ta (30 degrees C.) condition. Chronic dosing produced sensitization of both hyperthermic and hyperkinetic responses. The findings indicate that ambient temperature, water consumption and frequency of drug use affect the hyperthermia which follows MDMA administration.     

A field study of the ventilatory response to ambient temperature and pressure in sport diving

We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.     

Interrelationships of hippocampal electroencephalogram, visually evoked response, and behavioral reactivity to photic stimuli in rats.

Examined the averaged visually evoked responses (VERs) at the cortex, hippocampal slow-wave rhythms, and behavioral activity of 8 male albino Holtzman rats in response to repetitive series of photic stimuli under "nonappetitive" conditions (no contingencies attached to stimuli) and "appetitive" conditions (stimuli signaled delivery of food pellets). Habituation of behavioral reactivity to flashes was associated with elaboration of the VER and shift of hippocampal slow-wave activity from high toward low frequencies. Appetitive conditions which progressively increased behavioral reactivity to flashes reduced VER components and shifted hippocampal slow-wave patterns toward higher frequencies. Significant interrelationships among hippocampal EEGs, movement patterns, and "ascending" processes that act upon sensory channels (VERs) would appear to reflect phasic operations of brainstem and diencephalic arousal mechanisms. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin-containing neurons: lack of response to changes in body temperature in rats

Extremely small concentrations (1 ng/kg/min) of prostaglandins E1, A1, and A2 elevated arterial blood pressure in the rat when infused into the carotid artery. Similar infusions into the femoral vein failed to demonstrate a pressor response. Higher concentrations of the same prostaglandins infused into the femoral vein resulted in a significant depression of blood pressure.     

Lowering ambient or core body temperature elevates striatal MPP+ levels and enhances toxicity to dopamine neurons in MPTP-treated mice

The neuroprotective effects of lowering body temperature have been well documented in various models of neuronal injury. The present study investigated the effects a lower ambient or core body temperature would have on damage to striatal dopamine (DA) neurons produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice received systemic MPTP treatment at two different temperatures, 4 degrees C and 22 degrees C. MPTP-treated mice maintained at 4 degrees C demonstrated (1) a greater hypothermic response, (2) a significant reduction in striatal DA content and tyrosine hydroxylase (TH) activity, and (3) significantly greater striatal 1-methyl-4-phenylpyridinium (MPP+) levels, as compared to mice dosed with MPTP at room temperature. Parallel studies with methamphetamine (METH) were conducted since temperature appears to play a pivotal role in the mediation of damage to DA neurons by this CNS stimulant in rodents. As previously reported, METH-induced hyperthermia and the subsequent loss of striatal DA content were attenuated in animals dosed at 4 degrees C. We also evaluated the effects a hypothermic state induced by pharmacological agents would have on striatal neurochemistry and MPP+ levels following MPTP treatment. Concurrent administration of MK-801 or 8-OHDPAT increased the striatal MPP+ levels following MPTP treatment. However, only 8-OHDPAT potentiated the MPTP-induced decrements of striatal DA content and TH activity; MK-801 did not affect MPTP decreases in these striatal markers of dopaminergic damage. Altogether, these findings indicate that temperature has a profound effect on striatal MPP+ levels and MPTP-induced damage to DA neurons in mice.     

Obese binge eaters: Affect, cognitions, and response to behavioral weight control.

The present study compared obese female binge eaters and nonbinge eaters of comparable age and weight on mood, diet behavior, and responses to a standard versus modified behavioral weight-control program. The modified behavioral program emphasized meal regularity, intake of complex carbohydrates, and activity as an alternate to overeating. Binge eaters reported significantly more depressive symptomatology, psychological distress, and maladaptive diet behavior than nonbinge eaters at pretreatment and at all subsequent assessments. Furthermore, binge eaters were more likely to drop out of treatment. No differences in weight loss at posttreatment occurred between binge eaters and nonbinge eaters, but binge eaters regained significantly more weight than nonbinge eaters at 6-month follow-up. Differences in weight loss between the groups were not significant at the 1-year follow-up, and no significant differences between the standard and modified treatment conditions were observed. Marked differences between binge eaters and nonbinge eaters in affect and cognitions appeared to persist despite behavioral treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology

We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups.     

Differential behavioral response to dopamine D? agonists by sexually naive, sexually active, and sexually inactive male rats.

This study was performed with male rats categorized as sexually active (SN), sexually active (SA). or sexually inactive (SI). In a first experiment the effects of the dopamine (DA) D? agonist SND 919 (0.05, 1, and 10 mg/kg) on the copulatory behavior of SN, SA. and SI rats were assessed. In a second experiment the DA D? agonist B-HT 920 (0.2 mg/kg) was used, and examination was limited to SN and SA rats. The effects exerted on stretching-yawning, penile erection, and sedation by the same compounds at the same doses in these three rat categories were also investigated. The main findings were that SND 919 and B-HT 920 facilitated ejaculation in SA rats, and that the rats that were different as regards level of sexual activity exhibited different behavioral responses to the two DA agonists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tolerance and sensitization to the behavioral effects of cocaine in rats: relationship to benzodiazepine receptors

Tolerance and sensitization to the behavioral effects of cocaine were investigated in rats responding under a fixed-consecutive-number eight schedule of food reinforcement. The development of tolerance or sensitization was induced by delivering the drug either immediately before or after each behavioral session during chronic administration. Chronic cocaine administered before each session resulted in tolerance, as indicated by the shift to the right in the cocaine dose response curve. This tolerance was more likely to develop in the presence of an external discriminative stimulus. On the other hand, when cocaine was delivered after each session, the injections did not disrupt responding and sensitization or increased sensitivity rather than tolerance developed. This sensitization was more likely to occur when the external discriminative stimulus was not present. These data suggest that either tolerance or sensitization to the behavioral effects of cocaine can occur following the same number of chronic injections, with the effect dependent on the context under which the drug is delivered. Significant differences in benzodiazepine receptor binding measured autoradiographically using [3H]flumazenil were observed between rats that received cocaine before or after each session, suggesting that the development of tolerance and sensitization may be mediated through changes in benzodiazepine receptors in discrete brain regions.     

The influence of antibodies to TNF-alpha and IL-1beta on haemodynamic responses to the cytokines, and to lipopolysaccharide, in conscious rats

Male, Long Evans rats (350-450 g) were anaesthetized and had pulsed Doppler probes and intravascular catheters implanted to allow monitoring of regional (renal, mesenteric and hindquarters) haemodynamics in the conscious state. Our main objectives were to:- assess the effects of administering human recombinant tumour necrosis factor (TNF)-alpha and human recombinant interleukin-1 (IL-1)beta, alone and together; determine the influence of pretreatment with a mixture of antibodies to TNF-alpha and IL-1beta on responses to co-administration of the cytokines; ascertain if pretreatment with a mixture of the antibodies to TNF-alpha and IL-1beta had any influence on the responses to lipopolysaccharide (LPS). TNF-alpha (10, 100 and 250 microg kg(-1), in separate groups, n=3, 9 and 8, respectively) caused tachycardia (maximum delta, +101+/-9 beats min(-1)) and modest hypotension (maximum delta, -10+/-2 mmHg), accompanied by variable changes in renal and mesenteric vascular conductance, but clear increases in hindquarters vascular conductance; only the latter were dose-related (maximum delta, +6+/-6, +27+/-9, and +61+/-12% at 10, 100 and 250 microg kg(-1), respectively). IL-1beta (1, 10, and 100 microg kg(-1) in separate groups, n = 8, 8 and 9, respectively) evoked changes similar to those of TNF-alpha (maximum delta heart rate, +69+/-15 beats min(-1); maximum delta mean blood pressure, -14+/-2 mmHg; maximum delta hindquarters vascular conductance, +49+/-17%), but with no clear dose-dependency. TNF-alpha (250 microg kg(-1)) and IL-1beta (10 microg kg(-1)) together caused tachycardia (maximum delta, +76+/-15 beats min(-1)) and hypotension (maximum A, -24+/-2 mmHg) accompanied by increases in renal, mesenteric and hindquarters vascular conductances (+52+/-6%, +23+/-8%, and +52+/-11%, respectively). Thereafter, blood pressure recovered, in association with marked reductions in mesenteric and hindquarters vascular conductances (maximum delta, -50+/-3% and -58+/-3%, respectively). Although bolus injection of LPS (3.5 mg kg(-1)) caused an initial hypotension (maximum delta, -27+/-11 mmHg) similar to that seen with co-administration of the cytokines, it did not cause mesenteric or hindquarters vasodilatation, and there was only a slow onset renal vasodilatation. The recovery in blood pressure following LPS was less than after the cytokines, and in the former condition there was no mesenteric vasoconstriction. By 24 h after co-administration of TNF-alpha and IL-1beta or after bolus injection of LPS, the secondary reduction in blood pressure was similar (-16+/-2 and -13+/-3 mmHg, respectively), but in the former group the tachycardia (+117+/-14 beats min(-1)) and increase in hindquarters vascular conductance (+99+/-21%) were greater than after bolus injection of LPS (+54+/-16 beats min ' and +439%, respectively). Pretreatment with antibodies to TNF-alpha and IL-1beta (300 mg kg(-1)) blocked the initial hypotensive and mesenteric and hindquarters vasodilator responses to co-administration of the cytokines subsequently. However, tachycardia and renal vasodilatation were still apparent. Premixing antibodies and cytokines before administration prevented most of the effects of the latter, but tachycardia was still present at 24 h. Pretreatment with antibodies to TNF-alpha and IL-1beta before infusion of LPS (150 microg kg(-1) h(-1) for 24 h) did not affect the initial fall in blood pressure, but suppressed the hindquarters vasodilatation and caused a slight improvement in the recovery of blood pressure. However, pretreatment with the antibodies had no effect on the subsequent cardiovascular sequelae of LPS infusion. the results indicate that although co-administration of TNF-alpha and IL-1beta can evoke cardiovascular responses which, in some respects, mimic those of LPS, and although antibodies to the cytokines can suppress most of the cardiovascular effects of the cytokines, the antibodies have little influence on the haemodynamic responses to LPS, possibly because, during infusion of LPS, the sites of production and local action of endogenous cytokines, are not accessible to exogenous antibodies.     

Pancreatic duct cells in rats: secretory studies in response to secretin, cholecystokinin-pancreozymin, and gastrin in vivo

In rats given a copper-deficient diet plus penicillamine to destroy the acinar tissue selectively, the sensitivity and secretory pattern of pancreatic duct cells to a variety of hormones has been investigated. Resting flow rate of this pancreatic duct model was in the same range as in the intact gland. The duct cells responded to increasing doses of secretin by producing more juice with increasing outputs of bicarbonate, sodium, potassium, and chloride. Bicarbonate concentration increased with the lowest dose of secretin up to values of 64 mEq per liter and did not further increase with higher doses of secretin and increasing secretory rates. The concentration of potassium increased with increasing doses of secretin and flow rates, whereas chloride concentration decreased in a reciprocal fashion to bicarbonate. Gastrin and cholecystokinin-pancreozymin did not significantly stimulate the duct cells. Atropine did not inhibit the action of secretin on the flow rate or on bicarbonate secretion.