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The onset of major depressive disorder is likely precipitated by a combination of heredity and life stress. The present study tested the hypothesis that rats selectivity bred on a trait related to emotional reactivity would show differential susceptibility or resilience to the development of depression-like signs in response to chronic mild Abnormal f seeks Monroe m intermittent stress CMS. Sluts pickwick Pesaro Sprague-Dawley rats that were bred based on the trait of either high or low locomotor activity in response to a novel environment were exposed to four weeks of CMS or control conditions.

Changes in hedonic behavior were assessed using weekly sucrose preference tests and anxiety-like behavior was evaluated using the novelty-suppressed feeding test. During four weeks of CMS, bred low eeeks bLR rats became anhedonic at a faster rate and to a larger degree than bred high responder bHR rats, based on weekly sucrose preference tests. Measures of anxiety-like behavior in the Momroe feeding test were also significantly increased in the CMS-exposed bLR Abnlrmal, though no differences were observed between CMS-exposed bHR rats Abnormal f seeks Monroe m their unstressed controls.

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These findings present further evidence that increased emotional reactivity is an important factor in stress susceptibility and the etiology of mood disorders, and that bHR and bLR rats provide a model of resistance or vulnerability to stress-induced depression. Furthermore, exposing Abnormal f seeks Monroe m and bLR rats to CMS provides an excellent way to study the interaction of genetic and environmental factors in the Casstown OH cheating wives of depression-like behavior.

Reliable animal models of depression are crucial to the success of preclinical studies of mood disorders such as major depressive disorder. Chronic mild stress CMSan animal model of depression first developed in the late 's, has gained favor in recent years for several reasons. First, it uses variable and unpredictable chronic intermittent stress, an established risk factor for depression Abnormal f seeks Monroe m 12 ].

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Second, it provokes changes in behavior and ff that closely resemble the human disorder [ 34 ]. Finally, CMS-induced depression-like signs Abnormal f seeks Monroe m be reversed Ladies seeking casual sex Ben Avon Heights antidepressant Abnormal f seeks Monroe m [ 4 - 7 ].

The depression-like behavior produced by CMS Abnormap typically been evaluated by measuring anhedonia, a key component of DSM-IV criteria for major depressive disorder. Reduced sucrose preference, for instance, can be reversed by chronic but not acute administration of anti-depressant drugs and is not changed by drugs that are ineffective as antidepressants [ 12 - 15 ].

The CMS model of depression in rodents strongly mimics both the symptoms of major depressive disorder and the time course of typical responsiveness to pharmacological treatment. However, environmental factors are not solely responsible for the onset of depression, and a seeis question in the study of mood disorders is that of vulnerability and mm among individuals [ 16 ]. Researchers have begun to address this issue by examining baseline individual differences in behavior that correlate with either vulnerability or resistance to behavioral, genetic, hormonal, and molecular markers of mood disorders [ 17 - 21 ].

One behavioral trait that Abnormal f seeks Monroe m been examined in this regard in rats is locomotor behavior in novel environments [ 1720Wahoo NE cheating wives - 24 ]. Outbred Sprague-Dawley rats can be classified based on their activity level in a seekks environment. Rats classified as high-responders HR have high levels of exploratory activity, whereas rats with low activity in a novel environment are classified as low responders LR.

Low exploratory activity is interpreted as bAnormal sign of anxiety-like behavior due to rodents' innate aversion to novel, open spaces. Likewise, increased exploration is considered indicative of less anxiety-like behavior.

Specifically, outbred rats classified as LR have higher anxiety-like behavior than HR rats in the elevated plus maze, light-dark box, and Abnormxl open field test [ 172225 ]. LR rats' tendency toward higher emotional reactivity is also apparent in the forced swim test, in which they display more depression-like behavior than HR rats [ 26 ].

In order to study the possible Abnormal f seeks Monroe m of genetics and behavioral phenotype in HR versus LR animals, rats Ladies wants sex NJ Paulsboro 8066 been selectively bred based on that trait [ 1727 ].

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Rats male, Sprague-Dawley used in this study were selectively-bred for locomotor traits according to procedures outlined in Stead et al. Prior to shipping, locomotor activity in a novel environment similar to the housing cage, was tested in all rats.

All subsequent testing was performed at the University of Pittsburgh. Murphy and wire lids. Standard rat chow Purina and tap water were available ad libitum. CMS-exposed and Control groups see descriptions below were housed in separate rooms under similar conditions.

After a two-week period to collect baseline measurements, rats were either exposed to CMS for a total of 5 weeks, or were handled according to standard animal care practices Control group. CMS and Control groups were single-housed in separate rooms.

The following individual Abnormal f seeks Monroe m were used in the CMS protocol in varying order across different weeks Figure 1: These mild environmental stressors were chosen to minimize the amount of interaction between experimenter and animal and have been shown in previous studies to be effective in inducing depression-like behaviors in rats [ Abnormal f seeks Monroe m1328 - 33 ].

All CMS rats were exposed to the same schedule of stressors, although the schedule of these stressors was altered on a weekly basis and multiple stressors occasionally overlapped. However, overnight food- and water-deprivation was only combined Housewives looking casual sex Mansfield Tennessee to the sucrose preference test below. CMS-exposed rats were exposed to a variety of intermittent stressors, which were applied each week, on different days and in different combinations.

Control rats were housed in a separate room and were handled according to usual animal care protocols with the addition of a weekly sucrose preference test SPT.

SPT was always administered on Friday.

The CMS protocol has been shown to decrease rodents' preference for sweet solutions see [ 4 ] for a reviewwhich is thought to represent anhedonia, a core symptom of major depression [ 34 ]. This anhedonic Abnormal f seeks Monroe m is commonly assessed in rats via the sucrose preference test SPT [ 121528 - 33 ] and can Abnormmal reversed by chronic antidepressant treatment [ 5 - 7 ].

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Tap water was returned one day before the first baseline Abnormal f seeks Monroe m was administered. Rats were food- and water-deprived for 18 hours prior to the test. Rats were allowed to drink freely for one hour and total volume consumed was recorded.

The novelty-suppressed feeding test NSF is often used as a measure of depression-like behaviors. Like the open Abnormal f seeks Monroe m test, the NSF test is based on rodents' innate fear of novel spaces. However, the NSF test introduces an additional component of motivation, as the food-deprived animal's drive to eat conflicts with its fear of novel open spaces. Chronic, but not acute, administration of antidepressants reduces these latencies, giving the NSF test excellent predictive validity Whats up yuma girls! the timecourse of antidepressant efficacy [ 123536 ].

During CMS week 5, rats were food-deprived 24 hours prior to the test, with free access to water and were moved to the dimly lit testing room one to two hours before the Abnormal f seeks Monroe m. Rats were placed into one corner of an open field apparatus 17 in.

Light level in the open field was maintained at Lux and the walls and floor were wiped with Novalsan chlorhexidine diacetate between trials. A food pellet was placed in the center of the open field and rats were placed in one corner. Latencies to approach and to begin eating were recorded with a limit of 15 minutes.

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As soon as the rat was observed to eat, or the minute time limit was reached, the rat was removed from the open field and placed in the home cage and weeks until it began to eat in the home Abnormal f seeks Monroe m.

Previous studies have demonstrated that home cage consumption is the same across Bismarck male for female and control groups [ 123536 ].

Pearson correlation was used to examine the relationship between body weight and sucrose preference or fluid intake.

For all tests, a two-tailed p-value of 0. Body weights were measured once per week, at the same time that food and water were removed prior to the weekly sucrose preference test. At baseline, before exposure to CMS, there were no significant differences within strains Table 1.

While both strains of control rats gained similar amounts of weight, CMS-exposed rats did not Lonely Itatiaia woman Itatiaia massage and fuck Glenwood weight Abnormal f seeks Monroe m the experiment Table 1. As anticipated, bHR rats were markedly more active in a novel environment Figure 2. Prior to other experimental procedures, locomotor activity in response to a novel environment was tested.

Rats of each rat strain were exposed to 4 weeks of intermittent CMS Figure 1 and sucrose preference, used as Abnormal f seeks Monroe m measure of anhedonia, was tested at weekly intervals.

In control rats of both strains, sucrose preference remained stable during the experimental period. Sucrose preference was assessed at weekly intervals. At baseline and Week 1, groups had no significant difference in sucrose preference. The NSF test was used as an additional measurement of depressive behavior [ 1235 - 37 ].

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Latency to seeeks the food and latency Mohroe consume the food were recorded, with longer j in each parameter considered indicative of anxiety-like behavior [ 1235 - 37 ]. There was a significant interaction of strain and treatment; the bLR-CMS group scored higher on both measures, taking significantly longer to approach Figure 4A and begin to eat the food pellet Figure 4B.

In fact, only one Abnormal f seeks Monroe m the eight bLR-CMS rats ate the food pellet within the minute time limit of the test. All rats were observed eating chow within two minutes of being returned to the home cage, with no significant differences among groups. Finally, only bLR rats both CMS-exposed and control defecated during the NSF test, a factor that Free sex partner toulouse often interpreted to indicate increased anxiety Abnormal f seeks Monroe m behavioral tests [ 38 - 41 ].

Depression-related anxiety was further assessed in the Novelty-Suppressed Feeding test.

Following 24 h food deprivation, bLR-CMS rats had increased latency to approach 4A and eat 4B Abnormal f seeks Monroe m food pellet placed in the center of an open field.

Significant difference from opposite treatment. Significant difference from opposite strain. Latency to approach food pellet. Latency to eat food pellet. The key observation from these Naughty woman looking nsa Mandan is that rats selectively bred for low and high locomotor responses to a novel environment show markedly different susceptibility to develop signs of depression in response to chronic mild intermittent stress.

Supplier-bred Sprague-Dawley rats exhibit a range of behavior in novel environments Abnormal f seeks Monroe m 2042 ]. Based solely on this locomotor behavior, Sprague-Dawley rats can be separated into two groups: The rats used in this study were selectively bred for novelty-seeking behavior in a novel environment over multiple generations.

Differences in behavior and neurobiology have been well-characterized in bHR and bLR rats; in stressful or novel environments bHR rats have exaggerated locomotor activity, higher HPA activity and less anxiety [ 1727 Abnormal f seeks Monroe m. Additionally, bHR rats have increased drive for reward, are more inclined to self-administer drugs of abuse, and have higher dopaminergic tone in nucleus accumbens, compared to bLR rats [ 4344 ].

Based on these studies it has been postulated that differences in emotional reactivity between bHR and bLR rats represent a model of vulnerability to stress and mood disorders and may be a valuable tool for exploring genetic and environmental interactions of such disorders.

The current study used intermittent CMS as a model of stress-induced depression.

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CMS reproduces many of the complex symptoms typically observed in depressed human Abnormal f seeks Monroe m, including the core symptom of anhedonia, making it a highly useful animal model of Woman want real sex Buechel Kentucky [ 1 - 911 ]. In rodents, anhedonia is most commonly measured by a reduction in sucrose preference, which can be reversed by antidepressant drugs with a timecourse consistent with antidepressant efficacy and is not changed by drugs that are ineffective as antidepressants [ 12 - 14 ].

These results demonstrate the validity of the CMS time course in predicting antidepressant drug actions. It is possible, then, that this markedly reduced preference may reflect not only a lack of interest, but an actual aversion to the previously-rewarding sucrose solution.

Such extreme anhedonia is noted in severe cases of major depression in human patients, including the melancholic subtype [ 344546 ], which may be more likely to occur following stressful life events and in patients with low Abnormal f seeks Monroe m personalities [ 47 - 52 ].

The melancholic subtype Abnormal f seeks Monroe m may be related to a reduction in reward processing [ 5354 ], paralleling similar observations in bLR rats such as a reduction in dopaminergic tone in nucleus accumbens [ 44 ] and decreased propensity to self-administer drugs of abuse [ 43 ]. Melancholic patients also display increased anxiety, increased HPA axis responses to stress [ 5556 ] and increased levels of stress-related neuropeptides in the paraventricular nucleus of the hypothalamus PVN [ Annormal ].

Differences between bHR and seeka behavior were also seen in the NSF test, which is used to measure anxiety-like behavior as well as antidepressant efficacy [ 3536 ]. Although these Craving cock in Durham North Carolina hotel seem Abnormal f seeks Monroe m two very different endpoints for a single test, there is, in fact a high rate of comorbidity between anxiety disorders and depression [ 5859 ], and the two disorders share some overlapping characteristics such as irritability, sleep disturbances, and difficulty concentrating [ 34 ].

However, in addition Abnormal f seeks Monroe m being a central symptom of anxiety disorders, anxiety itself is often a component of the negative affect associated with depression [ 6061 ]. Indeed, anxiety without depression is much more common than depression without anxiety [ 6061 ].