Are Wistar-Kyoto rats a genetic animal model of depression resistant to antidepressants?

Lahmame, Abdeljalil; Arco, Carmen del; Pazos, Ángel; Yritia, Mercedes; Armario, Antonio

doi:10.1016/s0014-2999(97)01276-4

Cited by 134 publications

(83 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exposure to the FST can also alter the density of monoamine receptors and their regulation by antidepressant drug treatments (Duncan et al 1985;Paul et al 1990). However, there were no major differences in the densities of 5-HT 1A , 5-HT 2 or ␤ -adrenergic receptors reported in WKY rats when compared with other rat strains, either at baseline, in response to stress, or after drug treatment (Paré and Tejani-Butt 1996;Lahmame et al 1997). Exposure to the FST is also known to produce changes in the release of dopamine, norepinephrine, and serotonin in a variety of brain regions, and these effects interact with antidepressant drug treatments (Rosetti et al 1993;Kirby and Lucki 1997).…”

Section: Discussionmentioning

confidence: 77%

“…However, these results disagree with those of Lahmame, Armario, and associates. These investigators reported that WKY rats were subsensitive in their response to the acute administration of desipramine or imipramine in the FST, although they did respond to chronic treatment with imipramine (15 mg/kg, once daily for 14 days) (Lahmame and Armario 1996;Lahmame et al 1997). A number of procedural differences might contribute to the discrepant results between Lahmame and those of Paré and ourselves, although both laboratories use FST scoring procedures that measure active behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…It would be interesting to examine changes in the FST in WKY rats produced by chronic administration of different types of antidepressants (c.f. Detke et al 1997), because chronic administration of imipramine altered FST performance in WKY rats (Lahmame et al 1997). Although WKY rats were responsive to desipramine, WKY rats showed a significantly reduced response to the serotonergic antidepressant fluoxetine, causing only small and inconsistent effects of swimming behavior up to 40 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

López‐Rubalcava

Lucki

2000

Neuropsychopharmacology

316

154

View full text Add to dashboard Cite

-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...

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

López‐Rubalcava

Lucki

2000

Neuropsychopharmacology

316

154

View full text Add to dashboard Cite

show abstract

“…On the other hand, 14 day DES treatment had no such effect on LCA suggesting a short duration of DES effect on LCA if any. In addition, WKY rats, as a putative animal model of depression, may not respond to selective serotonin uptake inhibitors (SSRI) such as fluoxetine or paroxetine (Griebel et al, 1994;Lahmame et al, 1997;Lopez-Rubalcaava and Lucki, 2000;Tejani-Butt et al, 2003). Thus, other animal models are necessary to explore not only the effectiveness of antidepressants but also possible neurochemical bases of the behavioral changes induced by chronic alcohol use.…”

Section: Discussionmentioning

confidence: 99%

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Getachew¹,

Hauser²,

Taylor³

et al. 2008

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive-and anxietylike behaviors induced by alcohol were blocked by daily treatment with a tricyclic antidepressant. It may be suggested that prophylactic treatment of alcoholics with an antidepressant prior to detoxification may improve treatment outcome for alcoholism.

show abstract

“…It this context, it is noteworthy that on acute, but not repeated administration, WKY rats are resistant to the anti-immobility effect of the nonselective 5-HT reuptake inhibitor, imipramine, in the forced swim test (Lahmame et al 1997). In the latter case, serotonergic, but also noradrenergic systems may be involved as WKY rats (and SHRs) are resistant to the antiimmobility effect of the noradrenaline reuptake inhibitor desipramine (Lahmame and Armario 1996).…”

Section: Strain-related Differences In the Behavioural Effects Of Citmentioning

confidence: 99%

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

Pollier

Sarre

Aguerre

et al. 2000

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

Are Wistar-Kyoto rats a genetic animal model of depression resistant to antidepressants?

Cited by 134 publications

References 47 publications

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

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

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

Contact Info

Product

Resources

About