Rats selectively-bred for behavior related to affective disorders: Proclivity for intake of alcohol and drugs of abuse, and measures of brain monoamines

Weiss, Jay M.; West, Charles H.K.; Emery, Milburn S.; Bonsall, Robert W.; Moore, Jason W.; Boss-Williams, Katherine A.

doi:10.1016/j.bcp.2007.09.027

Cited by 36 publications

(35 citation statements)

References 52 publications

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“…The depression-like phenotypes of SwLo rats (ie, low activity in the forced swim test that is reversible by chronic but not acute antidepressant treatment, decreased response to dopaminergic drugs Weiss et al, 2008;West et al, 1999a, b;West and Weiss, 1998)) have been described previously. Here, we show that SwLo rats have increased acute susceptibility to seizures induced by chemoconvulsants and electroshock, and also show exacerbated epileptogenesis in the chronic pilocarpine model and certain parameters of electrical kindling.…”

Section: Discussionmentioning

confidence: 76%

“…Although the focus of this study was on the SwLo rats as a model for susceptibility to epilepsy and depression, the SwHi rats are also of interest. Because the depression-and epilepsy-like phenotypes of 'wild-type', non-selected rats tend to fall somewhere in between those of SwLo and SwHi rats (Tabb et al, 2007;Weiss et al, 1998;Weiss et al, 2008;unpublished data), the SwHi rats may be a model for co-morbidity resilience.…”

Section: Resultsmentioning

confidence: 99%

“…A subset of rats in each experiment were exposed to a swim test to confirm the persistence of this phenotype in each line, whereas the remaining littermate animals were experimentally naive. On average, SwLo rats typically float for a minimum of 600 s and struggle for no more than 10 s of a 15-min test, whereas SwHi rats float for less than 20 s and struggle in excess of 200 s (Weiss et al, 2008). No differences in seizure susceptibility were observed between the swim test-exposed and naive rats, and data were combined.…”

Section: Selectively Bred Ratsmentioning

confidence: 99%

“…For example, norepinephrine depletion accelerates the development of hippocampal kindling and increases carbachol-induced wet dog shakes in rats, whereas central injection of norepinephrine decreases wet dog shakes (Ferencz et al, 2001;Kokaia et al, 1989;Turski et al, 1982; but see Bortolotto and Cavalheiro, 1986). These findings are of particular interest because SwLo rats have a selective decrease of norepinephrine in the hippocampus (Weiss et al, 2008), and chronic administration of norepinephrine reuptake inhibitors reverses depression-like phenotypes in SwLo rats in the swim test West and Weiss, 1998). Cholinergic dysfunction is another potential culprit.…”

Section: Potential Mechanisms Underlying the Swlo Seizure Phenotypesmentioning

confidence: 99%

“…Although several studies have assessed depression-like symptoms in epilepsy-prone animals (Jobe, 2003;Jones et al, 2008;McIntyre and Gilby, 2007;Pineda et al, 2011), there is only one study in which seizure susceptibility was assessed in an animal model of depression, the Swim LoActive (SwLo) rats (Tabb et al, 2007), which were selectively bred for low activity in a swim test and also exhibit other depression-like and anhedonic behaviors such as decreased response to dopaminergic drugs and increased intracranial self-stimulation threshold (Weiss et al, , 2008West et al, 1999a, b;C. West, personal communication).…”

Section: Introductionmentioning

confidence: 99%

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Seizure Susceptibility and Epileptogenesis in a Rat Model of Epilepsy and Depression Co-Morbidity

Epps

Tabb

Lin

et al. 2012

Neuropsychopharmacol

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Although a strong co-morbidity exists clinically between epilepsy and depression, the cause of this co-morbidity remains unknown, and a valid animal model is crucial for the identification of underlying mechanisms and the development of a screening tool for novel therapies. Although some rodent models of epilepsy have been reported to display behaviors relevant to affective disorders, the seizure susceptibility of animals prone to depression-like behavior has not been characterized. Toward this end, we assessed several forms of seizure sensitivity and epileptogenesis in rats selectively bred for vulnerability (Swim Lo-Active; SwLo) or resilience (Swim High-Active; SwHi) to depression-like phenotypes. The SwLo rats exhibit decreased motor activity in a swim test and other depression-like phenotypes, whereas the SwHi rats display increased motor activity in a swim test. SwLo rats exhibited a decreased latency to limbic motor seizures following acute pilocarpine administration in the absence of differences in pilocarpine pharmacokinetics, and also had a decreased threshold to tonic seizures induced by electroshock. Approximately half of the SwLo rats, but none of the SwHi rats, had spontaneous limbic motor seizures 5 weeks following pilocarpine-induced status epilepticus. While the number of stimulations required to achieve full amygdala and hippocampal electrical kindling were similar in the two rat lines, SwLo rats had a lower final hippocampal kindling threshold and more wet dog shakes during both amygdala and hippocampal kindling. Combined, these results indicate that SwLo rats are a model of epilepsy and depression co-morbidity that can be used for investigating underlying neurobiological and genetic mechanisms and screening novel therapeutics.

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Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Selectively Bred Ratsmentioning

confidence: 99%

Section: Potential Mechanisms Underlying the Swlo Seizure Phenotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Seizure Susceptibility and Epileptogenesis in a Rat Model of Epilepsy and Depression Co-Morbidity

Epps

Tabb

Lin

et al. 2012

Neuropsychopharmacol

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Rats bred for high anxiety exhibit distinct fear‐related coping behavior, hippocampal physiology, and synaptic plasticity‐related gene expression

et al. 2019

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The hippocampus is essential for learning and memory but also regulates emotional behavior. We previously identified the hippocampus as a major brain region that differs in rats bred for emotionality differences. Rats bred for low novelty response (LRs) exhibit high levels of anxiety‐ and depression‐like behavior compared to high novelty responder (HR) rats. Manipulating the hippocampus of high‐anxiety LR rats improves their behavior, although no work to date has examined possible HR/LR differences in hippocampal synaptic physiology. Thus, the current study examined hippocampal slice electrophysiology, dendritic spine density, and transcriptome profiling in HR/LR hippocampus, and compared performance on three hippocampus‐dependent tasks: The Morris water maze, contextual fear conditioning, and active avoidance. Our physiology experiments revealed increased long‐term potentiation (LTP) at CA3–CA1 synapses in HR versus LR hippocampus, and Golgi analysis found an increased number of dendritic spines in basal layer of CA1 pyramidal cells in HR versus LR rats. Transcriptome data revealed glutamate neurotransmission as the top functional pathway differing in the HR/LR hippocampus. Our behavioral experiments showed that HR/LR rats exhibit similar learning and memory capability in the Morris water maze, although the groups differed in fear‐related tasks. LR rats displayed greater freezing behavior in the fear‐conditioning task, and HR/LR rats adopted distinct behavioral strategies in the active avoidance task. In the active avoidance task, HRs avoided footshock stress by pressing a lever when presented with a warning cue; LR rats, on the other hand, waited until footshocks began before pressing the lever to stop them. Taken together, these findings concur with prior observations of HR rats generally exhibiting active stress coping behavior while LRs exhibit reactive coping. Overall, our current findings coupled with previous work suggest that HR/LR differences in stress reactivity and stress coping may derive, at least in part, from differences in the developing and adult hippocampus.

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Orexin, serotonin, and energy balance

Mavanji

Pomonis

Kotz

2021

WIREs Mechanisms of Disease

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The lateral hypothalamus is critical for the control of ingestive behavior and spontaneous physical activity (SPA), as lesion or stimulation of this region alters these behaviors. Evidence points to lateral hypothalamic orexin neurons as modulators of feeding and SPA. These neurons affect a broad range of systems, and project to multiple brain regions such as the dorsal raphe nucleus, which contains serotoninergic neurons (DRN) important to energy homeostasis. Physical activity is comprised of intentional exercise and SPA. These are opposite ends of a continuum of physical activity intensity and structure. Non-goal-oriented behaviors, such as fidgeting, standing, and ambulating, constitute SPA in humans, and reflect a propensity for activity separate from intentional activity, such as highintensity voluntary exercise. In animals, SPA is activity not influenced by rewards such as food or a running wheel. Spontaneous physical activity in humans and animals burns calories and could theoretically be manipulated pharmacologically to expend calories and protect against obesity. The DRN neurons receive orexin inputs, and project heavily onto cortical and subcortical areas involved in movement, feeding and energy expenditure (EE). This review discusses the function of hypothalamic orexin in energy-homeostasis, the interaction with DRN serotonin neurons, and the role of this orexin-serotonin axis in regulating food intake, SPA, and EE. In addition, we discuss possible brain areas involved in orexin-serotonin cross-talk; the role of serotonin receptors, transporters and uptake-inhibitors in the pathogenesis and treatment of obesity; animal models of obesity with impaired serotonin-function; single-nucleotide polymorphisms in the serotonin system and obesity; and future directions in the orexin-serotonin field.

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Rats selectively-bred for behavior related to affective disorders: Proclivity for intake of alcohol and drugs of abuse, and measures of brain monoamines

Cited by 36 publications

References 52 publications

Seizure Susceptibility and Epileptogenesis in a Rat Model of Epilepsy and Depression Co-Morbidity

Seizure Susceptibility and Epileptogenesis in a Rat Model of Epilepsy and Depression Co-Morbidity

Rats bred for high anxiety exhibit distinct fear‐related coping behavior, hippocampal physiology, and synaptic plasticity‐related gene expression

Orexin, serotonin, and energy balance

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