Selective Breeding of Rats for High and Low Motor Activity in a Swim Test

Weiss, Jay M.; Cierpial, Mark A.; West, Charles H.K.

doi:10.1016/s0091-3057(98)00075-6

Cited by 104 publications

(47 citation statements)

References 27 publications

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“…The nature of this variability, whether there are intrinsic differences in susceptibility to stress or differences in baseline locomotor activity, remains to be elucidated [1]. Our studies were in agreement with previous studies that have shown similar differences in mobility between inbred strains [14,19,35].…”

Section: Discussionsupporting

confidence: 91%

Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

Vieyra-Reyes¹,

Mineur²,

Picciotto³

et al. 2008

Brain Research Bulletin

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In this study, we compared the depression-like symptoms induced by olfactory bulbectomy (OBX) in the two inbred Wistar and Long Evans rat strains. We also analyzed the self-regulated oral intake of nicotine in these strains and the effect of nicotine on the depression-like symptoms of olfactory bulbectomy. Furthermore, we compared the antidepressant-like effects of nicotine on Wistar rats to those of transcranial magnetic stimulation (TMS), which has emerged as a therapeutic alternative for depression management.Our results show that Wistar rats develop depression-like symptoms, demonstrated by the forced swim test (FST), four weeks after OBX. However, we cannot observe these symptoms in bulbectomized Long Evans rats. Our results suggest that there are some innate differences in susceptibility to stress between these two rat strains.In Wistar rats, voluntary oral nicotine intake (1.2 mg/kg/day for 14 days) as well as nicotine administered as a single daily i.p. injection (1.5 mg/kg/day for 14 days) decrease the depression-like symptoms of OBX. Daily transcranial magnetic stimulation (TMS; 60 Hz and 0.7 mT for two hours per day for 14 days) also decreases depression-like symptoms but is less effective than nicotine.In conclusion, our results support the idea that there are possible innate differences for depression susceptibility and that nicotine and TMS may be useful in the treatment of this syndrome.

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Section: Discussionsupporting

confidence: 91%

Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

Vieyra-Reyes¹,

Mineur²,

Picciotto³

et al. 2008

Brain Research Bulletin

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“…Alterations in spontaneous activity are reported in various animal models of depression. For instance, locomotion is enhanced by olfactory bulbectomy and in BDNF conditional KO mice (Kelly et al, 1997;Monteggia et al, 2006), whereas it is reduced in the chronic mild stress, learned helplessness, and swim low-active models, as well as in Flinders rats and 5-HT transporter KO mice (Wagner et al, 1977;Overstreet, 1993;D'Aquila et al, 1994;Weiss et al, 1998;Ansorge et al, 2004). In our experiments, spontaneous locomotion and rearing were decreased in heterozygotes compared with WT controls.…”

Section: Discussionmentioning

confidence: 48%

Vmat2Heterozygous Mutant Mice Display a Depressive-Like Phenotype

Fukui¹,

Rodriguiz²,

Zhou³

et al. 2007

J. Neurosci.

136

144

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The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in humans, we investigated whether Vmat2 heterozygous (HET) mice present with depressive-like behaviors. The mutants showed locomotor and rearing retardation in the open field and appeared anhedonic to 1 and 1.5% sucrose solutions. Immobility times for Vmat2 heterozygotes were prolonged in forced swim and imipramine normalized this behavior. HET animals also showed enhanced immobility in tail suspension and this response was alleviated by fluoxetine, reboxetine, and bupropion. Stimulated GTP␥S binding indicated that ␣ 2 -adrenergic receptors in HET hippocampus were more sensitive to UK 14,304 (5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine) stimulation than in wild type (WT) mice. In learned helplessness, mice were exposed to a shuttle box for 4 d or were given inescapable foot-shocks for the same time period. On day 5, all animals were tested in shock escape. Failure rates and the latency to escape were similar for WT and HET mice that were only pre-exposed to the test apparatus. In foot-shock groups, learned helplessness was more robust in heterozygotes than in WT controls. Basal secretion of serum corticosterone was not distinguished by genotype; however, corticosterone levels in mutants were more responsive to stress. Anxiety-like responses of WT and HET animals in the open field, light-dark exploration, zero maze, and novelty-suppressed feeding tests were indistinguishable. Collectively, these findings suggest that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

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“…39 Another group bred SD based on activity in a 1-day FST and has produced low and high activity animals (SwLo and SwHi). 40,41 Swimming in the SwLo animals increases in response to drugs that affect dopamine neurotransmission. 42 Dopamine function appears to be altered in these animals, 42,43 making them useful for studying depressive symptoms related to dopamine function such as anhedonia.…”

Section: Discussionmentioning

confidence: 99%

Selectively bred Wistar–Kyoto rats: an animal model of depression and hyper-responsiveness to antidepressants

2003

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The Wistar-Kyoto (WKY) rat strain demonstrates endogenous hormonal and behavioral abnormalities that emulate many of those found in symptom-presenting depressive patients. Evidence suggests that the WKY strain may harbor heterogeneity not found in other inbred strains, including greater behavioral and genetic variability. We took advantage of this variability and selectively bred WKY for 'depressive' behavior using immobility in the forced swim test (FST) as a functional selector. Successive generations of selective breeding resulted in rats that exhibited the extremes of immobility in the FST: 'WKY most immobile' (WMI) and 'WKY least immobile' (WLI). Male WMI rats also showed significantly decreased activity in the open field test (OFT). Plasma corticosterone (CORT) response to restraint stress was significantly lower and less variable in WMI compared to WLI males. Subacute treatment of males with several classes of antidepressant had different effects on FST behavior in the two substrains. Both desipramine (10 mg/kg body weight), a tricyclic antidepressant, and phenelzine (7.5 mg/kg), a monoamine oxidase inhibitor, significantly and drastically decreased FST immobility in WMI. In contrast, WLI showed a limited response to these antidepressants. Neither substrain responded to fluoxetine (10 mg/kg), a selective serotonin reuptake inhibitor. These data show that selective breeding of WKY rats has resulted in two substrains with reduced variability and differing responsiveness to antidepressants, which represent a novel means to dissect the molecular mechanisms underlying depressive behavior. Molecular Psychiatry (2003) WKY rats are hyper-reactive to stress and show dysregulation of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes. We previously showed that compared to Wi rats, basal plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels of WKY rats remain significantly higher for several hours after the diurnal peak. 2 They also display increased steadystate levels of anterior pituitary pro-opiomelanocortin (POMC) mRNA and exaggerated plasma ACTH responses to acute and chronic stress compared to other rat strains. 3,4 A number of laboratories have found that WKY rats exhibit depressive-like behavior in a wide range of accepted behavioral paradigms. Increased immobility in the forced swim test (FST), considered as a measure of depressive-like behavior, 5-7 has been found in many studies. [8][9][10][11][12] Among other assessments of depressive or anxious behavior, WKY rats also show decreased activity in the open field test (OFT), a measure of anxiety/fear, 9,13 and in the defensive burying test (DB), a potential measure of passive coping. 9 Several studies have found that WKY rats show reduced responsiveness to tricyclic antidepressants (TCA) compared to Brown Norway, Lewis, Fisher 344 (F344), 11 and Sprague Dawley (SD) 14 rats, while others have reported increased responsiveness to TCA antidepressants. 15 Fluoxetine (selective serotonin reuptake inhibito...

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Selective Breeding of Rats for High and Low Motor Activity in a Swim Test

Cited by 104 publications

References 27 publications

Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

Vmat2Heterozygous Mutant Mice Display a Depressive-Like Phenotype

Selectively bred Wistar–Kyoto rats: an animal model of depression and hyper-responsiveness to antidepressants

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