Biomedical subjects

W P Paré

Publications and source records attributed to W P Paré.

At least 19 recordsLinked to original sources

PubMed2006

Alcohol consumption alters dopamine transporter sites in Wistar-Kyoto rat brain.

Even though animal and human studies show alterations in dopamine transporter (DAT) sites after alcohol withdrawal, the role of DAT in influencing either alcoholic or depressive behavior has not been examined extensively. Given that the Wistar-Kyoto (WKY) rat is a putative animal model of depressive behavior, the present study examined the effects of chronic alcohol consumption on DAT sites in WKY versus Wistar (WIS) rats. Brains from both strains were sectioned for autoradiographic analysis of [3H]-GBR12935 binding to DAT sites after 24 days of alcohol exposure. The results indicated that WKY rats consumed a greater amount of alcohol (P < 0.001) than WIS rats did throughout the experiment. Autoradiographic analyses of discrete brain regions indicated that alcohol consumption increased DAT sites in a greater number of brain areas in WKY compared to WIS rats. In WKY rats, the binding of [3H]-GBR12935 to DAT sites was increased in the basolateral, central and lateral nuclei of the amygdala, lateral nucleus of the hypothalamus, olfactory tubercle, caudate-putamen, nucleus accumbens and substantia nigra (P < 0.05) and decreased in the ventromedial nucleus of the hypothalamus and the CA1 region of the hippocampus. In WIS rats, alcohol consumption increased DAT sites in the CA1 region of the hippocampus, basolateral nucleus of the amygdala, ventral tegmental area and substantia nigra, and decreased DAT sites in the lateral and ventromedial hypothalamus and dentate gyrus. These results indicate a strain dependent alteration in DAT sites which may be related to altered dopamine neurotransmission in select brain regions following alcohol consumption.

Alcohol Drinking↗

PubMed2001

The emergence test: effects of psychotropic drugs on neophobic disposition in Wistar Kyoto (WKY) and Sprague Dawley rats.

1. The Emergence Test (ET), a variation of the open field test in which the rat is not handled, and is purported to measure neophobia, was applied to Wistar Kyoto (WKY) and Sprague Dawley (S-D) rats. 2. While no-stress control WKY rats were less active in the ET, pre-treatment with shock stress exacerbated strain differences. WKY rats, previously exposed to shock, did not emerge from the home cage start box during repeated testing, whereas previously stressed S-D rats vacated the home cage quickly and revealed increasing behavioral agitation. 3. Diazepam reduced emergence latency only in S-D rats, whereas nomifensine significantly increased head poke responses in WKY rats. 4. WKY rats responded to the ET with characteristically depressive behavior, whereas S-D rats responded to the same ET with behavioral agitation and anxiety. The implications of these behavior patterns for discriminating between anxiety and depressive behavior are presented.

Animals↗

PubMed2000

Investigatory behavior of a novel conspecific by Wistar Kyoto, Wistar and Sprague-Dawley rats.

The assumption was made that investigatory behaviors (i.e., ano-genital and general body sniffing) of a female conspecific by a mature male rat, has positive hedonic characteristics. Because reduced interest in pleasurable events (i.e., anhedonia) is diagnostically related to depressive behavior, the hypothesis was advanced that less investigatory behavior would be observed in an animal model of depression, namely the Wistar Kyoto (WKY) rat strain. In Experiment 1, WKY, Wistar and Sprague-Dawley male rats were subjected, in the first test series, to three consecutive 2-min exposures to one intruder stimulus female, followed later by another three consecutive 2-min exposures to a second stimulus intruder female. On the second test series, 24 h later, the male rats were exposed to one female for 2 min, followed 6 min later to another 2-min exposure to another stimulus female. Half the male subjects were subjected to tail shock stress 2 h before the first test series. All males demonstrated a habituation of the investigatory response to the same stimulus female, but a dishabituation when subsequently exposed to a new stimulus female. Only WKY rats, exposed to prior stress, revealed a significant reduction in investigatory behavior. In Experiment 2, using only WKY and Wistar rats, a factorial design was used to observe any differences between two stressors, namely tail shock and water restraint, and also to observe possible differences in investigatory behavior towards male vs. female intruder rats. Restraint stress and shock stress elicited significant reductions in investigatory behavior for WKY rats, but not Wistar rats, when confronted with female intruder rats. Male intruders elicited more freezing behavior, as well as aggressive defensive fighting behavior from resident male rats. The results are interpreted to suggest that the significant decrease in investigatory behavior towards a female intruder, which was observed primarily in stressed WKY males, reflects the presence of anhedonia in stressed WKY rats, and reinforces our assertion that the WKY rat strain represents a useful animal model of depressive behavior.

Animals↗

PubMed1999

Negative affect and voluntary alcohol consumption in Wistar-Kyoto (WKY) and Sprague-Dawley rats.

Based on the assumption that the Wistar-Kyoto (WKY) rat strain represents an animal model for depressive behavior, the purported relationship between depression and alcohol consumption was investigated in three experiments. WKY rats consumed more alcohol than Sprague-Dawley (S-D) rats when offered a choice between a 7% alcohol solution and tap water. Subsequently, the severity of stress-induced stomach ulcers was significantly less in WKY rats that had access to alcohol. In Experiment 2, WKY and S-D rats were assigned to either an alcohol access treatment or to a water-only treatment for 27 days and subsequently observed in the open-field test (OFT) and the elevated plus-maze (EPM). Access to alcohol reduced response latency in the OFT, and increased the percent time in the open arm and the total number of arm entries in the EPM for WKY rats. In Experiment 3, the antidepressant, imipramine, reduced alcohol consumption in both strains and significantly increased percent time in the open arms of the EPM for WKY rats. These studies support the assumption that depression and alcohol consumption may be related.

Alcoholism↗

PubMed1997

Differences in the stress response of Wistar-Kyoto (WKY) rats from different vendors.

Wistar-Kyoto (WKY) rats are hyperresponsive to stress and prone to stress ulcer. However, some variability in these general findings has been reported. This variability may reflect differences in the rat stock from different WKY rat vendors. WKY rats from Taconic (WKY-T), Harlan Sprague-Dawley (WKY-H), and Charles River (WKY-CR) were observed in the open-field test (OFT) and the forced-swim test (FST), and subsequently exposed to ulcerogenic water-restraint stress. There were no differences between vendor stocks in the FST, but WKY-CR rats were significantly more immobile in the OFT as compared to WKY-T and a Wistar control group. WKY-CR and WKY-H rats revealed significantly more ulcers as compared to WKY-T and Wistar rats. The WKY inbreeding programs at Charles River and Harlan, as compared to the outbreeding practice at Taconic may contribute to these vendor differences. These data indicate that WKY rat sublines from different vendors represent an important source of variability when comparing studies of stress reactivity using WKY rats.

Animals↗

PubMed1997

Effect of acute or repeated stress on behavior and brain norepinephrine system in Wistar-Kyoto (WKY) rats.

WKY rats develop more restraint-induced gastric ulcers and exhibit more depressive behavior compared to other rat strains. Exposure to novel stressors for 21 days exacerbates depressive behavior in WKY rats and alters beta-adrenoceptors (beta-ARs) and norepinephrine transporter (NET) sites in several limbic brain regions when compared to Sprague-Dawley rats. The present study examined whether these effects would be elaborated following an acute stressor and whether WKY rats would demonstrate adaptation after repeated stress. Rats were subjected to a 2-h supine restraint stress for either one or eight consecutive daily sessions. Open-field behavioral data were collected immediately after the daily stress sessions. Brains were sectioned for autoradiographic analysis of 125I-pindolol binding to beta-ARs and 3H-nisoxetine binding to NET sites in discrete brain regions. Acute 1-day stress resulted in a significant drop in body weight and an inhibition of behaviors in the open field. These effects were also sustained following 7 days of chronic restraint stress. In contrast, while acute stress had no effect on NET binding sites or beta-ARs, repeated stress decreased NET sites in the amygdala, hypothalamus, and locus coeruleus with little effect on beta-ARs in the brain regions examined.

Acute Disease↗

PubMed1996

Enhanced retrieval of unpleasant memories influenced by shock controllability, shock sequence, and rat strain.

The propensity to recall unpleasant events may be related to depression and posttraumatic stress disorder. This study examined the extent to which the recall of a previously unpleasant event (i.e., passive avoidance training) may be influenced by another aversive event. The other aversive event was tail shock. Since the Wistar Kyoto (WKY) rat strain has been proposed as an animal model of depressive behavior, this study was conducted with WKY and Wistar rats. Parameters manipulated included shock controllability, shock sequence (i.e., tail shock before avoidance training versus tail shock after training), and rat strain. Performance of the passive avoidance (PA) response was greater in WKY rats. Exposure to inescapable tail shock was related to greater PA performance compared to exposure to escapable or no-shock treatments. Tail shock prior to PA training led to a greater recall of the PA response. The magnitude of the PA response was influenced by the rat strain, shock controllability, and shock sequence. The applicability of these data to the memory bias phenomenon in depression is discussed.

Animals↗

PubMed1994

Effect of repeated novel stressors on depressive behavior and brain norepinephrine receptor system in Sprague-Dawley and Wistar Kyoto (WKY) rats.

This study compared the effects of repeated novel stressors on 'depressive behaviors', defined by the forced-swim and open-field tests, in Sprague-Dawley (S-D) and Wistar Kyoto (WKY) rats. Since stress appears to alter brain norepinephrine (NE) activity, this study also investigated the effects of the stressors on beta-adrenoceptors (beta-ARs), alpha 2-adrenoceptors (alpha 2-ARs) and NE transporter (NET) sites in S-D and WKY rats. Stress did not alter 125I-iodopindolol (125I-PIN) binding to beta-ARs, nor [3H]idazoxan ([3H]IDAZ) binding to alpha 2-ARs in S-D rats, compared to non-stressed controls. However, WKY-stressed rats showed a significant reduction in 125I-IPIN binding to beta-ARs in the cortex, hippocampus, amygdala and hypothalamus, and a reduction in [3H]IDAZ binding to alpha 2-ARs in the amygdala. [3H]nisoxetine ([3H]NIS) binding to NET sites in WKY-stressed rats was also reduced in the cortex, hippocampus and amygdala. When both strains were compared, the most surprising finding was a significantly higher density of NET sites in the hippocampus and amygdala in WKY rats compared to S-D rats. The results of this study indicate that stress, not only exacerbates depressive behavior in WKY rats, but also selectively alters beta-ARs, alpha 2-ARs and NET sites in limbic brain regions. Thus, the WKY strain may serve as a useful animal model for depressive behavior and for the investigation of novel antidepressant drugs.

Adrenergic alpha-Antagonists↗

PubMed1994

Hyponeophagia in Wistar Kyoto (WKY) rats.

Unconditioned suppression of feeding due to novelty (hyponeophagia) was studied in Wistar Kyoto (WKY), Lewis, Fischer 344, and Wistar rats. Fasted rats were given access to food either in home cages (controls) or to a single pellet fixed to the middle of a novel open field environment (experimental). The degree of feeding suppression was significantly greater in WKY rats compared to the other three strains. We suggest that this hyponeophagia resembles the reduced feeding frequently associated with behavioral depression, and that this behavior in WKY rats is another demonstration that this strain is very responsive to stressful stimulation and may serve as a useful animal model for depressive behavior.

Animals↗

PubMed1994

Open field, learned helplessness, conditioned defensive burying, and forced-swim tests in WKY rats.

Wistar Kyoto (WKY) and Wistar rats were observed in four tests; the open field test (OFT), the conditioned defensive burying (DB) test, and two tests which are considered animal models of depressive behavior, namely the Porsolt forced-swim test (FST) and the shuttlebox escape responding following exposure to inescapable shock, that is, learned helplessness (LH). The four tests were administered according to a semirandomized schedule to control for sequence effects. All rats were later exposed to water-restraint stress and stomachs were subsequently inspected for ulcers. Stress ulcer severity was greater in WKY rats. WKY rats, as compared to Wistar rats, were hypoactive in the OFT, did not engage in DB, rapidly acquired the LH task, and were significantly more immobile in the FST. The FST was positively correlated with behaviors in the LH procedure and, to a lesser degree, with DB, but these relationships were observed only with WKY rats, not Wistar rats. The data suggested that the use of WKY rats represented a more sensitive procedure for detecting possible relationships between putative animal models of depressive behavior.

Animals↗

PubMed1994

Restraint stress in biomedical research: an update.

Since the publication of our initial review of restraint stress in 1986, much work has continued with this technique, either as a tool for the investigation of other pharmacological, physiological, or pathologic phenomena or with restraint stress itself serving as the object of the study. As we noted in 1986, the major use of restraint has been for the induction of stress responses in animals and, more specifically, for the investigation of drug effects, particularly as they affect typical stress-related pathology--gastrointestinal, neuroendocrine, and immunological agents have been extensively studied. In compiling this update on restraint stress and its effects, we noted an increasing emphasis on central nervous system mechanisms in peripheral disease, especially gastrointestinal disease. In particular, many CNS-active agents have been tested for their effects on gastric and duodenal lesion formation and gastric secretion, including antidepressants, antipsychotics, anxiolytics, noradrenergic, serotonergic, dopaminergic, and peptidergic compounds. Some of these agents are especially active in the gastrointestinal tract even when administered centrally, further solidifying the concept of a brain-gut axis. The present update includes studies of: methods and procedures, pre-restraint manipulations, post-restraint/healing effects, and drug effects. In addition, a current bibliography of reports that have employed restraint is included.

Animals↗

PubMed1994

Strain differences in hypothalamic-pituitary-adrenal activity and stress ulcer.

Strain differences in stress responsiveness have been previously described, but specific components of the hypothalamic-pituitary-adrenal (HPA) axis responsible for stress hypo- or hyperactivity have not yet been characterized. This study proposed to analyze the effect of restraint stress on different measures of HPA function and stress ulcer in stress-ulcer prone Wistar-Kyoto (WKY) and Fisher 344 (F-344) rats and in the ulcer-resistant Wistar strain. Adult male rats of these strains were sham adrenalectomized, adrenalectomized, and adrenalectomized-replaced with corticosterone pellet. Ten days after surgery, animals were subjected to the 2-h ulcerogenic water-restraint stress and killed 2 h later. Intact WKY rats had dramatically more ulcers and higher anterior pituitary adrenocorticotropic hormone (ACTH) and proopiomelanocortin mRNA levels than the other two strains. In WKY rats, adrenalectomy increased ulcer incidence but did not affect thymus weight, ACTH content, or hypothalamic corticotropin-releasing factor mRNA levels, in contrast to the profound effects of adrenalectomy on these parameters in the other strains. Furthermore, corticosterone replacement was either without effect or enhanced the effect of adrenalectomy on these parameters in WKY rats, while it reversed the effects of adrenalectomy in the other strains. These data imply that WKY rats respond to stress with enhanced and prolonged changes in peripheral functions that are regulated by glucocorticoids, suggesting the presence of impaired efficacy of the glucocorticoid negative feedback on HPA function.

Adrenalectomy↗

PubMed1993

Reduced incidence of stress ulcer in germ-free Sprague Dawley rats.

Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.

Analysis of Variance↗

PubMed1993

Passive-avoidance behavior in Wistar-Kyoto (WKY), Wistar, and Fischer-344 rats.

In Experiment 1, Wistar-Kyoto (WKY), Wistar, and Fischer-344 (F-344) rats were tested on two passive-avoidance tasks: a platform step-down task and a one-way avoidance task. Wistars had shorter response latency scores in the step-down task, whereas F-344 rats had shorter scores in the one-way task. A subsequent ulcerogenic water-restraint stress produced significantly fewer ulcers in Wistar rats as compared to WKY and F-344 rats. In Experiment 2, rearings, grooming, ambulation, defecation, and response ambivalence behaviors were recorded in the one-way avoidance task in addition to response latency. WKY rats defecated more and produced lower scores on the three activity measures as compared to Wistar and F-344 rats. Response latency and ambivalence scores were higher for WKY rats. The subsequent ulcerogenic procedure also produced more ulcers in WKY rats. These data verify the ulcer susceptibility of WKY rats and underscore the assertion that their predominant stress coping behaviors are immobility and freezing. High ambivalence scores in WKY rats suggest behavioral inhibition, which is readily elicited by stressors. These behaviors resemble depressive behavior and suggest that WKY rat may be a useful animal model of depression.

Animals↗

PubMed1993

Sex differences and stress response of WKY rats.

Wistar Kyoto (WKY), Fischer-344 (F-344), and Wistar male and female rats during either proestrus-estrus or diestrus phases of the estrus cycle were exposed to the ulcerogenic procedure of water restraint. Both male and female WKY rats revealed significantly more stomach ulcers as compared to Wistar and F-344 rats of the same sex. No persistent sex difference was observed, but ulcer severity was more pronounced during the proestrus-estrus phase as compared to the diestrus phase of the estrus cycle particularly in WKY female rats. In the second study, WKY females were observed as more active in the open-field test (OFT), but more immobile in the forced swim test (FST), as compared to WKY male rats. In addition, proestrus-estrus WKY females were less active in the OFT and significantly more immobile in the FST as compared to diestrus females. Thus, proestrus-estrus WKY females were judged as more emotional in the OFT and as exhibiting more signs of behavioral depression according to the FST. These studies suggest that the steroid hormone milieu in WKY rats may be responsible for these behavioral changes as well as the stress responsiveness in this stress-susceptible rat strain.

Animals↗

PubMed1993

Depressive behavior and stress ulcer in Wistar Kyoto rats.

Wistar Kyoto (WKY) rats, as compared to several other rat strains, are hypoactive in the open field test and in the defensive burying test. WKY rats readily acquire a learned helplessness task as well as a passive avoidance tasks. WKY rats also reveal a greater susceptibility to restraint-induced stress ulcer. The behavioral tests suggest the presence of depressive behavior in WKY rats. When exposed to the Porsolt forced-swim test of 'behavioral despair', WKY rats are judged as exhibiting more depressive behavior. Desipramine not only reduced immobility in the forced-swim test, but also diminished the severity of restraint-induced stress ulcer. These data suggested a heightened activity of the hypothalamic-pituitary axis. Basal plasma ACTH levels did not differ between WKY rats and Wistar rats, but serial plasma ACTH response to restraint stress was significantly greater for WKY rats. These data suggest that depressive behavior is a characteristic of WKY rats and this strain is a valuable model for studying depression which may be induced by an exaggerated stress response.

Animals↗

PubMed1992

The performance of WKY rats on three tests of emotional behavior.

The behavior of Wistar, Fischer-344, and WKY male rats was observed on three tests of emotional behavior. These included the defensive-withdrawal test, the elevated plus maze, and the conditioned defensive-burying test. Rats were subsequently exposed to the water-restraint ulcerogenic procedure. Fischer-344 rats were more active in the defensive-withdrawal tests, but other behavioral measures in this test did not discriminate between the three strains. Scores reflecting anxiety in the elevated plus maze were lowest for Fischer-344 rats and highest for WKY rats, but the anxiety scores of WKY rats did not differ significantly from Wistar rats. The behavior of WKY rats was significantly different from the other two strains in the conditioned defensive burying test. While the degree of anxiety is measured by burying behavior, elicited by the novelty of prod shock, immobility was the prevalent response of WKY rats. WKY rats also revealed significantly higher ulcer severity scores when exposed to water-restraint stress after each behavioral test procedure. We propose that WKY rats are hyperresponsive to stress and that novelty stress elicits depression-like behavior, which is the prevalent behavioral stress response in WKY rats.

Agonistic Behavior↗

PubMed1990

Pavlov as a psychophysiological scientist.

It is suggested that Pavlov was not only a famous physiologist, but due to his work on the conditional reflex, he could be considered a behavioral scientist. In addition his work on experimental neurosis gives him the distinction of being a pioneer investigator in the area of psychological stress. Pavlov's research is viewed against a background of primitive research tools and unproductive subjective theories. Nineteenth century scientists who influenced Pavlov included Darwin, Botkin, Heidenhain, Gaskell and Bernard. Pavlov's research on the digestive system emphasized the role of the nervous system, launched the field of gastroenterology, and emphasized the concept of the conditional reflex. Pavlov's conditional reflex formulations were based on the theoretical formulations of Sechenov, and possibly the work of David Hartley. The discovery of secretin, by Bayliss and Starling, and its influence on the stomach led Pavlov to diminish his work on the digestive system and to focus his research on the conditional reflex phenomenon. Arguments which suggest that Pavlov worked as a behavioral scientist include his conceptual formulations, his research on traditional psychological topics and his investigation of psychiatric disorders. His conditioning research emphasized the individual differences of his animal subjects which led to his research on typology and experimental neurosis which formed the basis for his work on environmental stressors and psychopathology.

Conditioning, Classical↗