Social partnering alters sleep in fear-conditioned Wistar rats.

Social support, when provided following a traumatic experience, is associated with a lower incidence of stress-related psychiatric disorders. Our hypothesis was that providing a social interaction period with a naive conspecific would improve sleep architecture in response to cued fear conditioning in Wistar rats. Rats were randomly assigned to either the socially isolated or socially partnered groups.

Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood.

Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-D-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat.

Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

Background: While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors.

Methodology/principal Findings: The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats.

Social partnering significantly reduced rapid eye movement sleep fragmentation in fear-conditioned, stress-sensitive Wistar-Kyoto rats.

Negative emotionality affects sleep-wake behavior in humans and rodents, and the Wistar-Kyoto (WKY) rat strain is known for its stress-sensitive phenotype. Analyzing rapid eye movement sleep (REMS) microarchitecture by separating REMS into single (siREMS; inter-REM episode interval>3 min) and sequential (seqREMS; interval≤3 min) episodes, we previously reported that cued fear conditioning (CFC) increased REMS fragmentation in WKY compared to Wistar rats by increasing the number of seqREMS episodes. Since social support affects fear responsiveness in humans, we hypothesized that social interaction with a naive partner would affect the sleep-wake response to CFC in WKY rats.

Adolescent social defeat alters markers of adult dopaminergic function.

Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat.

Reduced γ range activity at REM sleep onset and termination in fear-conditioned Wistar-Kyoto rats.

Recent investigations of rapid eye movement sleep (REMS) continuity have emphasized the importance of transitions both into and out of REMS. We have previously reported that, compared to Wistar rats (WIS), Wistar-Kyoto rats (WKY) responded to fear conditioning (FC) with more fragmented REMS. Gamma oscillations in the electroencephalogram (EEG) are synchronized throughout the brain in periods of focused attention, and such synchronization of cell assemblies in the brain may represent a temporal binding mechanism.

Fear conditioning fragments REM sleep in stress-sensitive Wistar-Kyoto, but not Wistar, rats.

Pavlovian conditioning is commonly used to investigate the mechanisms of fear learning. Because the Wistar-Kyoto (WKY) rat strain is particularly stress-sensitive, we investigated the effects of a psychological stressor on sleep in WKY compared to Wistar (WIS) rats. Male WKY and WIS rats were either fear-conditioned to tone cues or received electric foot shocks alone.

Central monoamine levels differ between rat strains used in studies of depressive behavior.

Previous studies have shown that the Wistar-Kyoto (WKY) rat strain may be a genetic model of depression when their behaviors are compared to Sprague-Dawley (SD) or Wistar (WIS) rats. Significant differences in dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporter site densities have been reported when comparing WKY to both SD and WIS rats. Susceptibility of WKY rats to anxiety and depressive behavior may be related to underlying differences in monoamine levels in various regions of the brain.

Differential patterns of alcohol consumption and dopamine-2 receptor binding in Wistar-Kyoto and Wistar rats.

The Wistar-Kyoto (WKY) rat strain has been described as an animal model of depressive behavior that consumes significantly greater amounts of alcohol compared to the Wistar (WIS) rat strain. Since the mesolimbic dopamine (DA) type-2 (D2) receptors mediate reward-related behaviors, the present study measured the binding of [(125)I]-Iodosulpiride to D2 receptors in the brains of WKY versus WIS rats following 24 days of voluntary alcohol or water consumption. Alcohol consuming WKY rats showed a significant increase in D2 receptor binding in several regions of the mesolimbic and nigrostriatal systems.

N-methyl-d-aspartic acid receptors are altered by stress and alcohol in Wistar-Kyoto rat brain.

Previous studies have shown that the Wistar-Kyoto (WKY) rat strain is more sensitive to stressors and consumes significant quantities of alcohol under basal as well as stressful conditions when compared to other strains. Given that the glutamate neurotransmitter system has been implicated in depression and addiction, the goals of the present study were to investigate the effects of stress and stress-alcohol interactions on N-methyl-d-aspartate (NMDA) receptors in the rat brain. Thus this study measured the binding of [(3)H] MK-801 to NMDA receptors in the prefrontal cortex (PFC), caudate putamen (CPu), nucleus accumbens (NAc), hippocampus (HIP) and basolateral amygdala (BLA) in WKY rats in comparison to the Wistar (WIS) rat strain.

Voluntary alcohol consumption alters stress-induced changes in dopamine-2 receptor binding in Wistar-Kyoto rat brain.

The Wistar-Kyoto (WKY) rat has been proposed as an animal model of depressive behavior and exhibits hyper-responsiveness to stressful stimulation when compared to other rat strains. We have demonstrated that WKY rats consume 200% more alcohol under naïve conditions as compared to their outbred counterparts, Wistar (WIS) rats. The present study was designed to understand the influence of stress and alcohol consumption on central dopamine type-2 (D2) receptor sites in these two behaviorally distinct rat strains.

Strain differences in the distribution of N-methyl-d-aspartate and gamma (gamma)-aminobutyric acid-A receptors in rat brain.

Aims: Previous studies have shown that the Wistar-Kyoto (WKY) rat strain exhibits depressive symptoms such as anhedonia, psychomotor retardation, ambivalence and negative memory bias following exposure to stress. Given the involvement of excitatory glutamate and inhibitory gamma (gamma)-aminobutyric acid (GABA) signaling pathways in influencing depressive behavior, the present study investigated strain differences in the distribution of central N-methyl-d-aspartate (NMDA) and GABA(A) receptor sites in WKY compared to their inbred counterpart, Wistar (WIS) rats.

Main Methods: Quantitative autoradiographic analysis was used to map the binding and distribution of NMDA and GABA(A) receptors in various brain regions in WKY and WIS rats.

Strain differences in the expression of dopamine D1 receptors in Wistar-Kyoto (WKY) and Wistar rats.

The Wistar-Kyoto (WKY) rat is a stress-sensitive strain that is prone to depressive-like behavior in various experimental paradigms. While recent work has highlighted a role for dopamine (DA) in the pathology of depression, research on the WKY rat has also suggested that dysfunction of DA pathways may be an important component of the behavior in this strain. Previous work has demonstrated differential patterns of DA transporter sites, DA D2 and D3 receptors in WKY rats compared to control strains.

Strain differences in the distribution of dopamine (DA-2 and DA-3) receptor sites in rat brain.

The dopamine (DA) pathway mediates numerous neuronal functions which are implicated in psychiatric disorders. Previously, our lab investigated the status of the dopamine transporter in the Wistar-Kyoto rat, a purported rodent model of depressive behavior, and reported significant alterations in transporter binding sites in several brain regions when compared to control rat strains. Given that DA-2 and DA-3 receptors belong to the same class of DA receptors, are co-localized in the mesolimbic and nigrostriatal regions of the brain and function as autoreceptors, this study mapped the distribution of central DA-2 and DA-3 receptors in Wistar-Kyoto and Wistar rats.

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.

Antidepressant drug induced alterations in binding to central dopamine transporter sites in the Wistar Kyoto rat strain.

The Wistar Kyoto (WKY) rat has been proposed as an animal model of depressive behavior. Exposing WKY rats to stress stimulation produces symptoms such as anhedonia, psychomotor retardation, ambivalence and negative memory bias. Given the role of the mesolimbic dopamine (DA) system in cognitive, emotional and motivational behaviors, we previously examined the distribution of DA transporter (DAT) sites in the brains of WKY compared to Wistar (WIS) and Sprague-Dawley (S-D) rats.

Strain differences in the distribution of dopamine transporter sites in rat brain.

The Wistar Kyoto (WKY) rat has long been proposed as an animal model of depressive behavior. Exposure to stress produces symptoms such as anhedonia, psychomotor retardation, ambivalence, and negative memory bias. Autoradiographic studies have revealed significant differences in the density of norepinephrine transporter (NET) and serotonin transporter (5-HTT) sites in several brain regions in WKY rats compared to Sprague-Dawley (S-D) rats.

Strain-dependent modification of behavior following antidepressant treatment.

The effects of repeated antidepressant drug treatment on behavioral outcome in Wistar Kyoto (WKY) rats, a putative animal model of depressive behavior, were compared to Wistar and Sprague-Dawley (SD) rats. Rats were treated with desipramine (norepinephrine [NE] uptake blocker), nomifensine (NE and dopamine [DA] uptake blocker), paroxetine (serotonin [5-HT] uptake blocker) or saline, for 12 days. On Day 11, rats were tested in the Porsolt forced swim test (FST).

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.

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats.

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task.

Fetal alcohol exposure alters serotonin transporter sites in rat brain.

This study examined the effects of fetal alcohol exposure (FAE) on serotonin transporter (5-HTT) binding sites in the brains of developing male and female rat offspring using the technique of quantitative autoradiography. Time-pregnant dams were fed liquid ethanol diet, isocaloric diet without ethanol or normal rat chow. Male and female offspring were sacrificed at 21, 40 and 60 days of age, brains removed and sectioned for analysis of 5-HTT sites.

Differential expression of thyroid hormone receptor isoforms by thyroid hormone and lithium in rat GH3 and B103 cells.

Background: The interaction between lithium, a mood stabilizer, and the thyroid axis has been extensively studied; however, the regulation of thyroid hormone receptors by lithium is yet to be investigated.

Methods: To test whether lithium affects thyroid hormones at the receptor level, we examined the effects of lithium in combination with triiodothyronine (T3) on gene expression of thyroid hormone receptor isoforms in GH3 and B103 cells.

Results: The pattern of expression as well as the magnitude of regulation of the different thyroid hormone receptor isoforms appeared to be cell line specific.

Lithium administration affects gene expression of thyroid hormone receptors in rat brain.

Even though lithium has received wide attention in the treatment of manic depressive illness, the mechanisms underlying its mood stabilizing effects are not understood. Lithium is known to interact with the thyroid axis and causes hypothyroidism in a subgroup of patients, which compromises its mood stabilizing effects. Since lithium was recently reported to alter thyroid hormone metabolism in the rat brain, the present study investigated whether these effects were mediated through regulation of thyroid hormone receptor (THR) gene expression.

Reserpine modulates serotonin transporter mRNA levels in the rat brain.

Despite recent advances in determining central serotonin (5-HT) function, the basic aspects by which serotonin neurotransmission is controlled and regulated are still not understood. Since the serotonin transporter (5-HTT) is involved in terminating the action of 5-HT that is released from the presynaptic nerve terminal, the regulation of 5-HTT may be an important step in controlling 5-HT neurotransmission at the synaptic cleft. The present study investigated the effects of reserpine administration on 5-HTT gene expression as well as on tryptophan hydroxylase (TPH) expression in the rat brain.

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.