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

Paré, William P.

doi:10.1016/0031-9384(94)90097-3

Cited by 254 publications

(161 citation statements)

References 33 publications

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“…Interestingly, others have tagged the WKY rats as a possibly stress-sensitive strain (Pare and Redei 1993;Pare and Kluczynski 1997). Numerous reports have indicated that the WKY rats display high anxiety and low locomotion reactivity compared with other strains (Pare 1992a(Pare , b, 1993(Pare , 1994Dugovic et al 2000). Likewise, the WKY have been proposed as an animal model of depressive behavior because they consistently demonstrate exaggerated behavioral and physiologic responses to stress in a variety of situations when compared with other strains (Pare 1993(Pare , 1994.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous reports have indicated that the WKY rats display high anxiety and low locomotion reactivity compared with other strains (Pare 1992a(Pare , b, 1993(Pare , 1994Dugovic et al 2000). Likewise, the WKY have been proposed as an animal model of depressive behavior because they consistently demonstrate exaggerated behavioral and physiologic responses to stress in a variety of situations when compared with other strains (Pare 1993(Pare , 1994. Indeed, the WKY strain demonstrates higher levels of behavioral immobility at baseline in the forced swimming test (a rodent test sensitive to antidepressant drugs) and in open field (Pare 1994;Lopez-Rubalcava and Lucki 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, the WKY have been proposed as an animal model of depressive behavior because they consistently demonstrate exaggerated behavioral and physiologic responses to stress in a variety of situations when compared with other strains (Pare 1993(Pare , 1994. Indeed, the WKY strain demonstrates higher levels of behavioral immobility at baseline in the forced swimming test (a rodent test sensitive to antidepressant drugs) and in open field (Pare 1994;Lopez-Rubalcava and Lucki 2000). Thus, these rats possess a combination of behavioral and neurochemical (dopamine-related) characteristics that make them interesting models in their own right.…”

Section: Discussionmentioning

confidence: 99%

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Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Drolet

Proulx

Pearson

et al. 2002

Neuropsychopharmacology

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WKHA rats constitute a recombinant inbred rat strain derived by phenotypic selection of the progeny of hybrid F2 crosses between SHR and WKY rats. WKHA are normotensive and show some features of hyperactivity and of hyper-reactivity to stress, but their utility as model of attention deficit/hyperactivity disorder (ADHD) has not yetWistar-Kyoto-derived Hyperactive (WKHA) rats constitute an inbred strain that has been derived from the progeny of hybrid Wistar-Kyoto (WKY)/ Spontaneously Hypertensive Rats (SHR) F2 crosses. The WKHA rats were developed initially in 1980 by Hendley and associates in the attempt to remove a prominent behavioral abnormality (hyperactivity) from the hypertensive trait of SHR that had been fixed in this strain during intensive inbreeding (Hendley and Ohlsson 1991;Hendley 2000). Using cross-breeding of SHR with WKY followed by recombinant selected inbreeding, Hendley and Ohlsson (1991) (Deschepper et al. 1997). WKHA display marked locomotor hyperactivity and hyperreactivity to stress when compared with WKY. The activity score obtained with WKHA in an exploration test in a novel environment is much higher than the score observed in the WKY strain (Sagvolden et al. 1992). Moreover, the WKHA also seems to display "attentional problems" when compared with WKY (Sagvolden et al. 1992). Although these characteristics are reminiscent of those observed in children diagnosed with attention deficit disorder (ADHD), the utility of this strain as a potential model of ADHD has not received extensive experimental attention.Accordingly, the present study was conducted to assess the face validity of the WKHA strain as a model of ADHD. To do so, we compared the performance of WKHA to both WKY (genetic control) and Wistar (outbred control) strains in two behavioral tests. First, we measured activity levels of the three strains in an exploration test in a novel environment. Second, we examined the behavior of the three strains in the prepulse inhibition (PPI) test of the acoustic startle reflex. This test assesses sensorimotor gating, or the extent to which a weak acoustic stimulus draws cognitive processing away from a more pronounced acoustic stimulus (Ralph et al. 1999;Wood et al. 1998). Although there is considerable debate as to whether PPI reflects the operation of an attentional (as opposed to a preattentional) mechanism, it is clear that PPI is involved in stimulus selection or stimulus filtering, a process that appears to be aberrant in ADHD (Ralph et al. 1999). Moreover, some evidence also exists for a deficit in sensorimotor gating in a sub-population of ADHD children (Castellanos et al. 1996). A third reason justifying our use of the PPI test is that, like locomotor activity, sensorimotor gating is modulated by central dopaminergic substrates (Swerdlow et al. 1994), and there is extensive clinical evidence implicating alterations in dopaminergic function in the pathophysiology of ADHD (Pliszka et al. 1996).We also examined the extent to which the performances of the three strains in both the locom...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Drolet

Proulx

Pearson

et al. 2002

Neuropsychopharmacology

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“…One inbred rat strain, the Wistar-Kyoto (WKY) rat bred initially from the Wistar rat as the control strain for the spontaneously hypertensive rat or SHR (Okamoto and Aoki 1963), has been proposed as an animal model of depressive behavior (Paré 1989;Paré and Redei 1993;Marti and Armario 1996), because they consistently demonstrate exaggerated behavioral and physiological responses to stress across a variety of situations in comparison to other strains. The WKY strain is one of the most susceptible to developing learned helplessness (Wieland et al 1986;Paré 1994) (Paré 1993;Paré 1996), and demonstrate greater hypo neophagia; that is, the fear of feeding in a novel environment when hungry, than other rat strains (Paré 1994). As expected from this profile, WKY rats readily acquire passive avoidance behaviors, but they demonstrate deficits when emitting active avoidance or anxiety-related behaviors (Paré 1994).…”

mentioning

confidence: 99%

“…The WKY strain is one of the most susceptible to developing learned helplessness (Wieland et al 1986;Paré 1994) (Paré 1993;Paré 1996), and demonstrate greater hypo neophagia; that is, the fear of feeding in a novel environment when hungry, than other rat strains (Paré 1994). As expected from this profile, WKY rats readily acquire passive avoidance behaviors, but they demonstrate deficits when emitting active avoidance or anxiety-related behaviors (Paré 1994). Physiologically, the WKY strain is more susceptible to developing gastric ulceration to stress than other rat strains (Paré 1990(Paré , 1994, and they secrete higher levels of adrenocorticotropic hormone in response to restraint plus cold stress (Paré and Redei 1993).…”

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confidence: 99%

Strain Differences in the Behavioral Effects of Antidepressant Drugs in the Rat Forced Swimming Test

López‐Rubalcava

Lucki

2000

Neuropsychopharmacology

316

154

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-Kyoto (WKY) rats provide a model of stressinduced depressive behavior, because they show enhanced vulnerability to the effects of stressors. The present study examined differences in the behavioral response to different types of antidepressant drugs between WKY and SpragueDawley (SD) rats in the forced swimming test (FST). WKY rats displayed significantly greater immobility than SD rats during their exposure to the FST. The noradrenergic antidepressant, desipramine, produced a dose-dependent reduction of immobility and increase of climbing behavior in the SD rats. In WKY rats, desipramine reduced immobility at a lower dose and produced increases of both swimming and climbing behavior. The serotonergic compounds, fluoxetine and 8-OH-DPAT, produced dosedependent reductions of immobility and increases of swimming behavior in the FST in SD ratsThere has been interest in performance differences between different rodent strains on behavioral tests for antidepressants, because such differences may identify underlying constitutive factors that contribute to the vulnerability to clinical depression in humans. A number of authors have reported robust interstrain differences both in baseline performances and the response to antidepressant drugs in animal behavioral tests that are sensitive to antidepressant drugs (Porsolt et al. 1978; Van der Heyden et al. 1987;Overstreet et al. 1992;Paré, 1992;Armario et al. 1995). One inbred rat strain, the Wistar-Kyoto (WKY) rat bred initially from the Wistar rat as the control strain for the spontaneously hypertensive rat or SHR (Okamoto and Aoki 1963), has been proposed as an animal model of depressive behavior (Paré 1989;Paré and Redei 1993;Marti and Armario 1996), because they consistently demonstrate exaggerated behavioral and physiological responses to stress across a variety of situations in comparison to other strains. The WKY strain is one of the most susceptible to developing learned helplessness (Wieland et al. 1986;Paré 1994) (Paré 1993;Paré 1996), and demonstrate greater hypo neophagia; that is, the fear of feeding in a novel environment when hungry, than other rat strains (Paré 1994). As expected from this profile, WKY rats readily acquire passive avoidance behaviors, but they demonstrate deficits when emitting active avoidance or anxiety-related behaviors (Paré 1994). Physiologically, the WKY strain is more susceptible to developing gastric ulceration to stress than other rat strains (Paré 1990(Paré , 1994, and they secrete higher levels of adrenocorticotropic hormone in response to restraint plus cold stress (Paré and Redei 1993).The FST is a behavioral test in rodents that predicts the clinical efficacy of many types of antidepressant treatments (Porsolt et al 1977(Porsolt et al , 1978. This test induces the development of immobility when a rodent has been placed in a tank of deep water for an extended period of time and makes only those movements necessary to keep its head above water (Porsolt et al. 1977). The development of immobility is usually facilitated by prior...

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Pharmacological characterization of enantiomers of 8‐thiomethyl‐2‐(di‐n‐propylamino)tetralin, potent and selective 5‐HT_1Areceptor agonists

Foreman

Fuller

Leander

et al. 1995

Drug Development Research

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LY274600 and LY274601 are the S (-) and R ( + ) enantiomers, respectively, of 8-thiomethyl-2-(di-n-propylamino)tetralin . In in vitro studies, both enantiomers have high and selective affinity for the 5-HT,, receptor. However, LY274600 produced submaximal inhibition of forskolin-stimulated cyclase activity, which indicates that it is a partial agonist, whereas LY274601 produced maximal inhibition of cyclase activity, which indicates that it i s a full agonist in this model. Both of these enantiomers had potent in vivo pharmacological effects in rats that are characteristic of 5-HT,, receptor agonists including (1) a reduction of hypothalamic 5-HIAA levels, (2) an increase in serum corticosterone levels, (3) a reduction in hypothalamic 5-HTP accumulation after decarboxylase inhibition, (4) an induction of 5-HT,, behavioral responses, e.g., flat posture and lower lip retraction, and (5) a lowering of body temperature. In these general pharmacological tests, both compounds had a potency equal to or greater than 8-OH-DPAT but had a greater oral activity. LY274601 appeared to be either slightly more potent or efficacious than LY274600. In the drugdiscrimination studies using pigeons trained to identify the effects of 8-OH-DPAT, LY274601 was significantly More potent than LY274600, but both were less potent than 8-OH-DPAT. Both enantiomers restored full sexual reflex function to rats that had reduced sexual capacity. In rats with normal capacity for sexual reflexes but reduced performance, the enantiomers caused decreases in ejaculatory latencies and postejaculatory latencies and increases in copulatory efficiency and rate. No consistent differences between the enantiomers could be demonstrated in these estimates of total sexual performance, erectile capacity, and sexual drive. Both enantiomers increased punished responding at lower doses than were needed to decrease unpunished responding in pigeons, an effect that i s indicative of anxiolytic activity. LY274600, a partial agonist, produced a significantly greater change in punished responding than did LY274601, a full agonist. Both compounds induced dose-related decreases in immobility time and defecation rate in the rat forced swim model, which represent reductions in stress-induced "behavioral despair" and stress-induced gastrointestinal motility. Collectively, these pharmacological studies have shown that the substitution of a thiomethyl for the hydroxyl group at the 8 position o n the 2-(di-n-propylamino) tetralin structure 67

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

Cited by 254 publications

References 33 publications

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Strain Differences in the Behavioral Effects of Antidepressant Drugs in the Rat Forced Swimming Test

Pharmacological characterization of enantiomers of 8‐thiomethyl‐2‐(di‐n‐propylamino)tetralin, potent and selective 5‐HT_1Areceptor agonists

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

Cited by 254 publications

References 33 publications

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Strain Differences in the Behavioral Effects of Antidepressant Drugs in the Rat Forced Swimming Test

Pharmacological characterization of enantiomers of 8‐thiomethyl‐2‐(di‐n‐propylamino)tetralin, potent and selective 5‐HT1Areceptor agonists

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Pharmacological characterization of enantiomers of 8‐thiomethyl‐2‐(di‐n‐propylamino)tetralin, potent and selective 5‐HT_1Areceptor agonists