The effect of centrally administered CCK-receptor antagonists on food intake in rats

Cholecystokinin (CCK) receptors are classified as two subtypes, designated CCK(A) and CCK(B), and both subtypes are found in brain and peripheral tissues of rats. CCK-8 has been shown to act peripherally to reduce meal size, and this satiating action can be blocked by CCK(A)-receptor antagonists. Recent evidence suggests that, in addition to the peripheral action of CCK, central CCK mechanisms may also be involved in satiety. Central administration of proglumide, a mixed CCK-receptor antagonist (CCK(A) > CCK(B)) has been shown to increase food intake and block the satiating effect of peripherally administered CCK-8 (15). In an attempt to replicate and extend these results, rats were given injections of proglumide or selective CCK-receptor antagonists into the lateral ventricle prior to a peripheral injection of CCK-8 or saline. Only proglumide stimulated an increase in 30-min test meal intake and attenuated the satiating effect of CCK-8. Two selective CCK(A)-receptor antagonists, lorglumide and devazepide, did not increase intake significantly when given alone, and they did not attenuate the effect of peripherally administered CCK-8. The selective CCK(B)-receptor antagonist, L365,260, reduced intake at all doses tested except the lowest. The lowest dose did not increase intake when given alone and did not attenuate the inhibitory effect of CCK on test-meal intake. Finally, a combination of devazepide and L365,260 did not increase intake or block the effect of peripherally administered CCK-8. These results suggest that CCK released by neurons in the brain and acting on central CCK(A)- and CCK(B)-receptors is not necessary for the control of meal size or for the satiating effect of peripherally administered CCK-8 in rats under our experimental conditions.     

Cholecystokinin changes the duration but not the rate of licking in vagotomized rats.

Abdominal vagotomy markedly reduces or abolishes the inhibitory effect of cholecystokinin (CCK-8) on meal size. To investigate the rate and microstructure of licking underlying this phenomenon, licking was measured throughout a meal of milk in intact and vagotomized rats after intraperitoneal injections of isotonic saline or CCK-8. CCK-8 increased the slope of the decay of licking, decreased the efficiency of licking, and decreased the duration of licking in intact rats but had no effect on either the slope of the decay of licking or the efficiency of licking, but it increased the duration of licking in vagotomized rats. These results demonstrate that abdominal vagal nerves are necessary for CCK-8 to increase the rate of decay of licking, but nonvagal mechanisms mediate the effect of CCK-8 on duration of licking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of variation of the composition of CSF in the rat upon drinking of water and hypertonic NaCl solutions.

Infusing conscious unrestrained rats with either 0.5 M NaCl-CSF or 0.7 M sucrose-CSF into the lateral cerebral ventricle (IVT) at 38 μl/hr for 4 hr induced drinking. Although the infusates were nearly equiosmotic, water drinking during the 0.5 M NaCl-CSF was greater than during 0.7 M sucrose-CSF. However, IVT infusions of 0.7 M mannitol-CSF at rates of 9.4 μl/hr or 38 μl/hr for 4 hr or 10 μl/hr for 4 days failed to induce water drinking. Also, IVT infusion of 0.27 M mannitol-CSF at 38 μl/hr for 4 hr failed to significantly alter water drinking. CSF [Na] was reduced by IVT infusion of either 0.7 M sucrose-CSF or 0.7 M mannitol-CSF. In contrast, CSF [Na] was increased by 4-hr IVT infusion of 0.5 M NaCl in rats denied access to water during the infusion. Intake of 0.5 M NaCl was not altered significantly from control intakes by any of the above IVT infusions. It is concluded that water drinking in the rat may be initiated by stimulation of either a sodium sensitive sensor alone or with an osmoreceptor system and that species specific differences in the induction of both water drinking and hypertonic saline drinking are apparent. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The reaction of S-nitrosoglutathione with superoxide

The gut peptide glucagon-like peptide 1(7-36) amide (GLP-1) is released into the circulation after food intake. GLP-1 has been shown to have an incretin effect and inhibits gastrointestinal motility in humans. In rats, intracerebral administration of GLP-1 results in reduced food intake. Obese humans have been found to have an attenuated plasma GLP-1 response to a mixed meal. To approximate the physiologic state, GLP-1 or saline was administered intravenously and randomly at the beginning of a test meal served on a universal eating monitor to 6 obese subjects to test our hypothesis that GLP-1 influences termination of food intake (and thus food intake during a meal) and feelings of satiety in humans. As a marker for gastric emptying, 1.5 g acetaminophen was given at the start of the meal. Blood samples for analysis of acetaminophen, insulin, glucose, glucagon, and C-peptide were obtained. Hunger, fullness, and food choice were assessed with visual analogue scales and food-choice questionnaires. GLP-1 infusion resulted in a prolonged period of reduced feelings of hunger, desire to eat, and prospective consumption after the meal. The rate of gastric emptying was slower during infusion of GLP-1. Postprandial blood glucose concentrations were reduced during the GLP-1 infusion, but the amount of energy consumed, eating rate, and plasma concentrations of insulin, glucagon, and C-peptide were unchanged. GLP-1 given exogenously at the start of a meal did not seem to affect meal termination or the amount of food eaten. However, postprandial feelings of hunger decreased, suggesting that exogenous GLP-1 may influence feelings of hunger and satiety in humans.     

Nutritive expectancies mediate cholecystokinin's suppression-of-intake effect.

In previous studies of cholecystokinin's (CCK's) effect on consumption, physical features (e.g., taste, texture, and odor) of test meals were confounded with the nutritive expectancies elicited by those features. To separately assess the role of these two factors in supporting CCK's suppression-of-intake effect, we varied the caloric expectancies elicited by a flavored test solution, while holding constant its actual caloric density, as well as all other unconditioned stimulus features. On alternate days for a 12-day period, hungry rats drank grape or orange Kool-Aid (noncaloric) mixed with a caloric 5% ethanol solution; on the other days, they drank the alternate flavor mixed with plain water. In a subsequent choice test between the flavored solutions without ethanol, the ethanol-associated flavor (Ef) was preferred over the water-associated flavor (Wf). Two days later, the rats were injected with either cholecystokinin octapeptide (CCK-8; ip, 2 μg/kg) or isotonic saline, and then given access to their Ef or their Wf for 1 hr. Consumption of the Ef was supressed by CCK-8; intake of the Wf was unaffected. These results suggest that CCK-8's effectiveness in suppressing intake of a test meal may be treated not to the unconditioned stimulus features of that meal but to the nutritive expectations elicited by those features. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prolongation of intermeal interval by gastrin-releasing peptide depends upon time of delivery

We have previously shown that brief, vena caval infusion of gastrin-releasing peptide1-27 (GRP), delivered shortly (5 min) after the end of the first spontaneous nocturnal meal, significantly prolongs the postprandial intermeal interval (IMI) without affecting the size of the subsequent meal in freely-feeding rats. In the present study, we tested whether varying the time at which GRP was delivered during the IMI affected its ability to prolong the interval. Specifically, rats (n = 9), fed milk ad lib and with indwelling inferior vena caval catheters, were infused for 1 min with saline or 10 nmol/kg of GRP either 5, 15, or 30 min after the end of the first spontaneous nocturnal meal. Each received a single infusion on any given test day. Infusions and recording of individual licks were fully automated and computer-controlled. When delivered 5 or 15 min after termination of the first nocturnal meal, GRP significantly increased the IMI from a control level of 82 +/- 12 min to 111 +/- 13 min and 106 +/- 18 min, respectively. Infusion of GRP 30 min after meal termination did not significantly alter the IMI. No effect on the size of the subsequent meal was observed under any condition. These results are consistent with the hypothesis that endogenous GRP acts in conjunction with events occurring shortly after meal termination to extend the duration of the IMI.     

Effect of some gastrointestinal hormones on antral, small intestinal and caecal myoelectrical activity in the conscious miniature pig

The effect of i.v. infusion of gastrin (CCK-4), cholecystokinin (CCK-8) and pancreatic polypeptide (PP), 20 and 200 ng/kg/min for 1 h, on gastrointestinal electrical activity and arterial pressure was studied in conscious miniature pigs. During infusion of CCK-8 a transient hypertension was observed. In the antrum, the 3 peptides provoked an increase in slow wave activity and a decrease in spike activity. In the intestine, CCK-8 induced an increase in ileal spiking activity, whereas infusion of PP resulted in an increased frequency of long spike bursts in the caecum.     

A behavioral probe of the growth of intake potential during the inter-meal interval in the rat.

The rat's willingness to ingest glucose after an initial intraoral intake test was probed by beginning a 2nd intraoral intake test at variable durations (1–220 min). In Exp 1, after an initial meal of 12.5% glucose solution averaging 26.9?±?1.7 ml, the size of the 2nd (probe) meal of the same stimulus increased linearly from 4.0?±?0.9 ml after a 1-min delay to 15.4?±?2.7 ml after a 120-min delay. In Exp 2, intraoral intake of a more concentrated (37.5%) glucose solution rose more slowly as a function of delay from 2.4?±?2.7 ml to 4.9?±?0.6 ml. For each glucose concentration, the linear recovery function and a slope that depends on stimulus concentration are consistent with a role for gastric emptying during the delay in intake recovery. In Exp 3, rats ingested 12.5% or 37.5% glucose to satiety in an initial test and received, after a variable delay, either the same or the other concentration as the probe stimulus. The same volumes were ingested at each delay whether the glucose concentration of the probe stimulus was the same or was switched from that presented in the initial test. This result shows that the taste and caloric properties of the probe stimulus played no role in determining how much of it would be ingested… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enteral enhancement of glucose disposition by both insulin-dependent and insulin-independent processes. A physiological role of glucagon-like peptide I

Glucagon-like peptide I (GLP-I)(7-36) amide is secreted by intestinal L-cells in response to food ingestion. GLP-I is a potent insulin secretagogue and also inhibits glucagon release. In addition, when given to humans in pharmacological amounts, GLP-I increases glucose disposal independent of its effects on islet hormone secretion. To test the hypothesis that this extrapancreatic effect of GLP-I on glucose disposition is present at physiological levels of GLP-I, we performed intravenous glucose tolerance tests (IVGTTs) 1 h after the following interventions: 1) the ingestion of 50 g fat to stimulate GLP-I secretion or the ingestion of water as a control and 2) infusion of GLP-I to attain physiological levels or a control infusion of saline. The results of the IVGTTs were analyzed using the minimal model technique to determine the insulin sensitivity index (SI) and indexes of insulin-independent glucose disposition, glucose effectiveness at basal insulin (SG), and glucose effectiveness at zero insulin (GEZI), as well as the glucose disappearance constant (k(g)) and the acute insulin response to glucose (AIRg). These parameters were compared between conditions of elevated circulating GLP-I and control conditions. After ingestion of fat and infusion of synthetic hormone, plasma GLP-I increased to similar levels; GLP-I did not change with water ingestion or saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ca2+-independent phospholipase A2 contributes to the insulinotropic action of cholecystokinin-8 in rat islets: dissociation from the mechanism of carbachol

Insulin secretion induced by cholecystokinin-8 (CCK-8) was recently suggested to involve phospholipase A2 (PLA2) activation. In this study, we examined whether CCK-8 stimulates the Ca2+-independent form of PLA2 in isolated rat islets, in comparison with stimulation by the PLA2-activating cholinergic agonist carbachol. We found that CCK-8 (100 nmol/l; 5.6 mmol/l glucose) induces lysophosphatidylcholine accumulation from [3H]palmitate-prelabeled islets (170 +/- 39%; P = 0.003) as well as arachidonic acid (AA) efflux from [3H]AA-prelabeled islets (190 +/- 13%; P < 0.001), and that p-amylcinnamoylantranilic acid (ACA) (50 micromol/l)-mediated PLA2 inhibition reduces CCK-8-induced AA efflux (52 +/- 11%; P = 0.001) and insulin secretion (67 +/- 16%; P < 0.001). Neither the Ca2+ channel antagonist verapamil (100 micromol/l) nor the Ca2+ATPase inhibitor thapsigargin (1 micromol/l) affected CCK-8-induced AA efflux and insulin secretion. Furthermore, despite removal of extracellular Ca2+, CCK-8 still increased AA efflux (48 +/- 14%; P = 0.006) and insulin secretion (105 +/- 46%; P = 0.025). In contrast, carbachol (100 micromol/l)-stimulated AA efflux was reduced by verapamil by 36 +/- 6% (P < 0.001) and abolished by removal of extracellular Ca2+. Overnight protein kinase C (PKC) downregulation by 12-O-tetradecanoyl phorbol-13-acetate (TPA) (500 nmol/l) reduced CCK-8-induced AA efflux (45 +/- 12%; P = 0.003) and insulin secretion (40 +/- 16%; P = 0.020). No additive action regarding either AA formation or insulin secretion was seen by combining TPA overnight and ACA, which implies the involvement of an additional PLA2- and PKC-independent signaling mechanism. The results show that CCK-8, in contrast to carbachol, activates Ca2+-independent PLA2 in islets and that the PLA2-activating capacity of CCK-8 is partly PKC dependent. Hence, Ca2+-independent PLA2 seems important for the insulinotropic effect of CCK-8, but not for that of carbachol.     

Altered feeding responses in mice with targeted disruption of the dopamine-3 receptor gene.

Dopamine signaling has been implicated in the control of food intake and body weight. In particular, dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the dopamine-3 receptor (D?R) in the feeding responses to 2-deoxy-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D?R-/- mice. In other experiments, D?R-/- mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D?Rs chronically inhibit the effects of adiposity hormones, thereby contributing to a net anabolic state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraventricular insulin and the level of maintained body weight in rats.

To determine whether central insulin administration lowers the level around which body weight is regulated, insulin (6 mU/day) or saline was infused into the 3rd ventricles of 4 groups of rats. One insulin-infused and 1 saline-infused group were food-deprived for 3 days and were then returned to an ad lib feeding schedule. The other 2 groups were maintained on ad lib feeding throughout. Insulin-infused food-deprived rats lost weight at a significantly greater rate than saline-infused food-deprived rats. In ad lib fed rats, insulin infusion caused a significant reduction of food intake and weight relative to saline-infused controls. When formerly food-deprived rats were returned to ad lib feeding, they gained weight, and this was significantly more pronounced in the saline-infused than the insulin-infused group. The body weights of the two insulin-infused groups converged on a value approximately 9% below the average of the 2 saline infused groups. Findings suggest that the 3rd-ventricular infusion of insulin does not incapacitate the rats and that they can alter their food intake either upward or downward to attain a new weight. Results also support the hypothesis that direct administration of insulin into the brain determines the level of weight maintained by the animal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radioimmunoassay of cholecystokinin in human plasma

A sensitive radioimmunoassay for cholecystokinin (CCK) has been developed. Porcine CCK-33 was labelled by conjugation with 125I-hydroxyphenyl-propionic acid succinimide ester. Antibodies were raised against porcine CCK-33 covalently coupled to egg albumin. Plasma samples were extracted with 96% ethanol prior to assay. Free and bound hormone were separated by dextran-coated charcoal. The antibodies bound CCK-8 and CCK-33 with equimolar potency. The assay detection limit was 1 pmol/l plasma. Within and between assay coefficients of variation were +/- 12.7 and 13.0% at mean plasma CCK concentrations of 13.2 and 13.6 pmol/l. The concentration of CCK in 47 normal fasting subjects ranged from undetectable to 22 pmol/l. Ingestion of a mixed meal in 9 normal subjects increased the plasma concentration from 8.3 +/- 2.5 S.E. to 24.4 +/- 6.5 pmol/l.     

Angiomyolipomatous hamartoma of the tongue

To examine the role of the liver in lipopolysaccharide (LPS)-induced hypophagia, we investigated the effect of hepatic portal and vena cava infusions (1 mL/30 min) of LPS (100 microg/kg of body weight) on feeding in rats. LPS infusion significantly reduced food intake when administered via either the hepatic portal vein or the vena cava. Both the magnitude and time course of this hypophagia were similar regardless of the infusion route. As in previous experiments of ours in which LPS was administered by intraperitoneal (i.p.) injection, LPS reduced food intake by decreasing meal frequency, without affecting meal size or duration. The results suggest that peripherally administered LPS does not act primarily in the liver to reduce food intake.     

Transportin: nuclear transport receptor of a novel nuclear protein import pathway

The main purposes of this study were to investigate the best parameter for describing gallbladder emptying and whether gallbladder bile emptying should be induced with a bolus injection or continuous infusion of cholecystokinin-octapeptide (CCK-8). METHODS: Gallbladder emptying was measured by dynamic cholescintigraphy. Twelve healthy subjects and six patients with gallstones were examined twice with CCK-8 infusion cholescintigraphy, 0.3 ng CCK-8 kg per min for 60 min under identical circumstances. Another six healthy subjects randomly received bolus injection (0.04 microgram/kg) and infusion of CCK-8 (0.3 ng/kg per min for 60 min), respectively, during cholescintigraphy on two separate occasions. The choice of bolus dose was based on recommendations from the CCK-8 manufacturer. The infusion dose was chosen to produce plasma CCK concentrations similar to postprandial plasma CCK levels. RESULTS: A parameter of gallbladder emptying, mean ejection fraction (EF), was defined as 100% minus the area under the time-activity curve normalized to 100% and divided by the time interval from maximum to minimum counts per minute. This parameter proved superior to the well known parameters, EFmax. and EF30, in regard to reproducibility in healthy subjects. The slope of the regression line for the mean EF was 0.998 and the intercept value approximately 0% (p = 0.0001). The mean coefficient of variation was 4%. Apart from a higher mean coefficient of variation, similar reproducibility results were seen in the six patients. The measurements of EF30 in healthy subjects scattered more widely around the mean compared to the mean EF and EFmax, which indicates poorer ability to separate normal from abnormal gallbladder emptying. Intravenous bolus injection of CCK-8 resulted in incomplete gallbladder emptying with a mean EF value of 16% (s.d. 9%; range 7%-32%) compared to 49% (s.d. 7%; range 37%-57%) following CCK-8 infusion (p = 0.004). Abdominal discomfort was observed in all subjects after administration of the bolus injection, whereas no complaints were reported during infusion. CONCLUSION: Mean EF is the best parameter for describing gallbladder emptying. Moreover, slow infusion of a physiological dose of CCK-8 is preferable to induce gallbladder emptying because it results in more complete emptying and has no side effects.     

Effect of excitatory amino acid, dopamine, and oxytocin receptor antagonists on noncontact penile erections and paraventricular nitric oxide production in male rats.

In male rats, noncontact erections occur concomitantly with an increase in NO?- and NO?- in the paraventricular nucleus of the hypothalamus (PVN). In the present study, both responses were reduced by the blockade of PVN excitatory amino acid receptors by dizocilpine, (+)-MK-801(1 and 5 μg), but not by 6-cyano-7-nitro-quinoxaline-2,3-dione (5 μg) or (±)-2-amino-4-phosphono-butanoic acid (5 μg). Also ineffective when injected into the PVN were the dopamine antagonists SCH 23390 (5 μg), S(+)-raclopride (10 μg), and cis-flupenthixol (10 μg), and the oxytocin antagonist d(CH?)?Tyr(Me)2-Orn?-vasotocin (1 μg). However, when the last was given into the lateral ventricles, it reduced noncontact erections without modifying NO?- and NO?- increases. These results suggest that excitatory amino acid transmission increases in the PVN during noncontact erections. This may contribute to increased NO production in the PVN, and it may activate oxytocin neurons mediating this sexual response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of a duodenal glucose infusion on the relationship between plasma concentrations of glucose and insulin in dairy cows

The effects of duodenal infusion of glucose on the relationship between plasma concentrations of glucose and insulin and on milk composition were investigated in a crossover design. Eight dairy cows were continually infused with water (control) or glucose (1.5 kg/d). Cows received diets consisting of dehydrated whole-plant maize in restricted amounts to equalize the energy supply between treatments. Basal (before meal) plasma concentrations of glucose and insulin were increased, but concentrations of nonesterified fatty acids (NEFA) were decreased, by glucose treatment. During the first 2 h after feed distribution, plasma insulin increased, and plasma glucose and NEFA decreased, in both control and treated cows. Afterward, plasma glucose increased in treated cows but further decreased in control cows. The difference reached 8 mg/100 ml without any change in plasma insulin. During the meal, concentrations of growth hormones in plasma were inhibited to a similar extent in both groups. In response to intravenous glucose or insulin challenges, changes in plasma glucose, NEFA, and insulin stimulated by glucose were also very similar in both groups. In conclusion, duodenal infusion of glucose increased basal plasma concentrations of glucose and insulin, increased postprandial plasma glucose, and decreased NEFA without inducing insulin resistance. Glucose treatment did not change milk yield but decreased milk fat yield, mainly through a decrease in the yield of C18 fatty acids that were derived from circulating fatty acids. In the absence of insulin resistance, the decrease in the yield of C18 fatty acids might be attributed to an inhibition of adipose lipolysis or an increase in adipose lipogenesis.     

Scopolamine disruption of septo-hippocampal activity and classical conditioning.

Sixteen New Zealand White rabbits were implanted with multiple-unit recording electrodes in the hippocampus and lateral septum. Animals received either scopolamine hydrobromide (HBr) or scopolamine methylbromide (MBr, 1.5 mg/kg sc) prior to nictitating membrane conditioning. Slow wave analysis indicated that HBr reduced 5- to 8-Hz and increased 9- to 12-Hz hippocampal activity and increased 1- to 4-Hz activity in both hippocampus and lateral septum. Integrated unit activity from the HBr group showed suppression of responses in septum and hippocampus during learning, whereas the MBr group developed conditioned responses (CRs) in both structures. Behavioral findings indicated that HBr took longer to reach criterion (M?=?329.5?±?45.3) than MBr (M?=?120.2?±?16.0). This experiment showed that centrally active anticholinergic drugs alter the patterns of neuronal activity in the septo-hippocampal region that predict and accompany normal learning. Such drugs delay behavioral acquisition as well, a result suggesting a modulatory role for this brain system in the acquisition phase of classical conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of intravenous administration of apolipoprotein A-IV on patterns of feeding, drinking and ambulatory activity of rats

To characterize the anorectic effect of apolipoprotein A-IV (apo A-IV), we examined the effect of apo A-IV on the patterns of feeding, drinking and ambulation of rats fed ad libitum. A single dose of 200, 135 or 60 micrograms was infused intravenously through a chronically indwelling right atrial catheter just before the dark period. Apo A-IV suppressed food intake by decreasing meal size, but did not affect the interval between meals, the speed of eating, or the latency to eat the first meal after infusion. The anorectic effect of apo A-IV was dose-dependent and was effective for about 3 h after the infusion. The anorectic effect of apo A-IV is specific because inactivation of apo A-IV abolishes its anorectic effect. The anorectic effect of apo A-IV is not shared by apo A-I. Apo A-IV had no effect on drinking behavior or ambulatory activity. The results seem to indicate that apo A-IV specifically decreases the meal size, which supports our hypothesis that apo A-IV may act as a physiological signal for satiation after the ingestion of a lipid meal.     

Relations between feeding and sleep patterns in the rat.

A concomitant analysis of sleep and feeding patterns in 11 male Wistar rats was carried out over 8 days, using continuous EEG recording. The proportion of slow-wave sleep and paradoxical sleep within an intermeal interval was constant and varied only in relation to the time of the day. During the dark period only, there were significant correlations between meal size and amount of time spent in both stages of sleep in the following intermeal interval. These correlations were even stronger between meal size and sleep duration in the intermeal interval that followed the next meal. Circadian variations in satiety ratios (i.e., units of subsequent intermeal interval and sleep per units of food ingested) and in deprivation ratios (i.e., units of feeding per units of prior intermeal interval and sleep) suggest that division of 24-hr data into 3 8-hr periods rather than 2 12-hr periods reveals distinct correlations between meal size and pre- and postmeal sleep and might reflect more accurately the underlying metabolic events. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)