Altered hormone levels and circadian rhythm of activity in the WKY rat, a putative animal model of depression

2001 ◽  
Vol 281 (3) ◽  
pp. R786-R794 ◽  
Author(s):  
Leah C. Solberg ◽  
Susan Losee Olson ◽  
Fred W. Turek ◽  
Eva Redei

The Wistar Kyoto (WKY) rat is hyperreactive to stress and exhibits depressive-like behavior in several standard behavioral tests. Because patients with depressive disorders often exhibit disruptions in the circadian rhythm of activity, as well as altered secretory patterns of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid hormones, we tested the hypothesis that these phenomena occur in the WKY rat. Plasma ACTH and corticosterone levels remained significantly higher after the diurnal peak for several hours in WKY rats relative to Wistar rats. Also, plasma levels of thyroid-stimulating hormone were significantly higher in WKY relative to Wistar rats across the 24-h period, despite normal or slightly higher levels of 3,5,3′-triiodothyronine. In addition, under constant darkness conditions, WKY rats exhibited a shorter free running period and a decreased response to a phase-delaying light pulse compared with Wistar rats. In several ways these results are similar to those seen in other animal models of depression as well as in depressed humans, suggesting that the WKY rat could be used to investigate the genetic basis for these abnormalities.

1978 ◽  
Vol 235 (4) ◽  
pp. H361-H366 ◽  
Author(s):  
J. T. Crofton ◽  
L. Share ◽  
R. E. Shade ◽  
C. Allen ◽  
D. Tarnowski

Because vasopressin is one of the most potent naturally occurring pressor agents, and because of its importance in the regulation of blood volume and composition, we have undertaken a study of the role of vasopressin in the pathogenesis of the hypertension in the Okamoto-Aoki spontaneously hypertension (SH) rat. In SH rats, systolic blood pressure increased from 135 +/- 3 (SE) mmHg at age 33 days to 184 +/- 3 mmHg at age 75 days (P less than 0.01). In the Wistar-Kyoto (WKY) control rats, blood pressure increased from 100 +/- 2 to 120 +/- 2 mmHg (P less than 0.01). The differences in blood pressure between the SH and WKY rats at all ages were significant (P less than 0.01). During the age period 33-75 days, the 24-h urinary excretion of vasopressin in the SH rat was consistently more than twofold greater (P less than 0.01) than in the WKY rat. Plasma vasopressin concentration and pituitary vasopressin content were also elevated in the SH rat (P less than 0.01 and P less than 0.02, respectively). Changes in systolic blood pressure in the SH rat, however, were not paralleled by changes in the urinary excretion of vasopressin. The data indicate that the secretion of vasopressin is elevated in the SH rat. However, the magnitude of this elevation, in and of itself, may not be sufficient to account for the rising blood pressure in the young SH rat.


1994 ◽  
Vol 266 (3) ◽  
pp. R960-R965 ◽  
Author(s):  
J. Ma ◽  
S. Aou ◽  
T. Hori ◽  
J. Ding

The effects of water-restraint stress on blood calcium levels and gastric pathology and their behavioral relevance were examined in Wistar-Kyoto (WKY) and Wistar rats. The stress induced more severe hypocalcemia (0.32 mM decrease) and gastric lesions (34.6 mm in mean length) in WKY rats than in Wistar rats (0.19 mM and 17.7 mm, respectively). The magnitude of hypocalcemia correlated positively with that of gastric lesions in both strains (WKY, r = 0.59; Wistar, r = 0.69). In the forced-swimming test, WKY rats exhibited a longer immobility time (6.53 min) and a shorter struggling time (0.54 min) than Wistar rats (3.33 and 1.90 min, respectively). The severity of hypocalcemia and gastric lesions correlated positively (r = 0.59 and 0.69, respectively) with the length of immobility time in the WKY rats, while it correlated negatively (r = -0.70 and -0.61, respectively) with the length of struggling time in the Wistar rats. These results suggest that stress-induced hypocalcemia and gastric lesions are closely related and are also influenced by behavioral responsiveness in a strain-dependent manner.


1995 ◽  
Vol 268 (6) ◽  
pp. R1500-R1506 ◽  
Author(s):  
W. J. Lee ◽  
E. K. Yang ◽  
D. K. Ahn ◽  
Y. Y. Park ◽  
J. S. Park ◽  
...  

The role of brain angiotensin II (ANG II) in mediating cardiovascular, vasopressin, and renin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) and Wistar rats. Intracerebroventricular administration of losartan (10 micrograms) and saralasin (1 microgram.microliter-1.min-1) produced a markedly greater fall in blood pressure and a reduced tachycardia during and after hemorrhage (15 ml/kg) compared with the artificial cerebrospinal fluid control in SHR and Wistar rats but not in WKY rats. Vasopressin release after hemorrhage was also impaired, but renin release was enhanced by intracerebroventricular ANG II antagonists in SHR and Wistar rats but not in WKY rats. Losartan and saralasin produced remarkably similar effects on the cardiovascular, vasopressin, and renin responses to hemorrhage. These data suggest that brain ANG II acting through AT1 receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage. The relative importance of brain angiotensin system may vary in different strains of rate.


2021 ◽  
Vol 22 (4) ◽  
pp. 1599
Author(s):  
Katarzyna Głombik ◽  
Jan Detka ◽  
Bartosz Bobula ◽  
Joanna Bąk ◽  
Magdalena Kusek ◽  
...  

The role that thyroid hormone deficiency plays in depression and synaptic plasticity in adults has only begun to be elucidated. This paper analyzes the possible link between depression and hypothyroidism in cognitive function alterations, using Wistar–Kyoto (WKY—an animal model of depression) rats and control Wistar rats under standard and thyroid hormone deficiency conditions (propylthiouracil administration—PTU). A weakening of memory processes in the WKY rats is shown behaviorally, and in the reduction of long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 hippocampal regions. PTU administration decreased LTP and increased basal excitatory transmission in the DG in Wistar rats. A decrease in short-term synaptic plasticity is shown by the paired-pulse ratio measurement, occurring during hypothyroidism in DG and CA1 in WKY rats. Differences between the strains may result from decreases in the p-CaMKII, p-AKT, and the level of acetylcholine, while in the case of the co-occurrence of depression and hypothyroidism, an increase in the p-ERK1-MAP seemed to be important. Obtained results show that thyroid hormones are less involved in the inhibition of glutamate release and/or excitability of the postsynaptic neurons in WKY rats, which may indicate a lower sensitivity of the hippocampus to the action of thyroid hormones in depression.


2004 ◽  
Vol 286 (4) ◽  
pp. H1229-H1235 ◽  
Author(s):  
Ernesto A. Aiello ◽  
María C. Villa-Abrille ◽  
Eduardo M. Escudero ◽  
Enrique L. Portiansky ◽  
Néstor G. Pérez ◽  
...  

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 ± 0.03 mg/g, n = 41) was intermediate between SHR (2.82 ± 0.04 mg/g, n = 47) and Wistar rats (1.98 ± 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.


2021 ◽  
Author(s):  
Aishwarya Segu ◽  
Nisha N Kannan

The circadian clock governs the timing of sleep-wake cycles as well as of other behavioural, physiological and metabolic processes. While the endogenous circadian clock mediates the timing of sleep, homeostatic mechanisms modulate the amount and depth of sleep. Evidence from previous studies showed that caffeine intake promotes wakefulness, whereas adult-stage specific caffeine treatment not only suppresses sleep but also delays the phase of circadian rhythm in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on circadian and homeostatic regulation of sleep. In the present study we examined the differential effect of acute and chronic caffeine treatment on sleep ontogeny as well as on circadian and homeostatic regulation of sleep in Drosophila. The results of our study showed that acute caffeine treatment reduces day and night sleep in mature flies through the homeostatic pathway whereas it reduced only the day sleep in young flies. Chronic caffeine treatment did not exert any significant effect on sleep in young flies. On the other hand, it delayed the timing of sleep in mature flies and in addition flies under higher caffeine concentration reduced the morning and evening anticipatory activity under 12 hour: 12 hour light: dark cycles. These flies also exhibited either a longer free running period or arrhythmicity under constant darkness. The results of our study showed that acute caffeine treatment suppresses sleep through the homeostatic pathway whereas prolonged caffeine treatment disrupts the circadian rhythm in mature flies.


1984 ◽  
Vol 247 (2) ◽  
pp. R250-R256
Author(s):  
H. G. Scholubbers ◽  
W. Taylor ◽  
L. Rensing

Membrane properties of whole cells of Gonyaulax polyedra were measured by fluorescence polarization. Circadian changes of fluorescence polarization exist in exponentially growing cultures. They show an amplitude larger than that of stationary cultures, indicating that a part of the change is due to or amplified by an ongoing cell cycle. Measurements of parameters of the circadian glow rhythm were analyzed for possible correlation with the membrane data. Considerable differences (Q10 = 2.5-3.0) in fluorescence polarization were found in cultures kept at different temperatures ranging from 15 to 27.5 degrees C. The free-running period length at different temperatures, on the other hand, differed only slightly (Q10 = 0.9-1.1). Stationary cultures showed higher fluorescence polarization compared with growing cultures, whereas the free-running period lengths did not differ in cultures of various densities and growth rates. Temperature steps of different sign changed the fluorescence polarization slightly in different directions. The phase shift of 4-h pulses (-5, -9, +7 degrees C) resulted in maximal phase advances of 4, 6, and 2 h, respectively. The phasing of the phase-response curves was identical in all these experiments, a finding not to be expected if the pulses act via the measured membrane properties. Pulses of drugs that change the fluorescence polarization (e.g., chlorpromazine and lidocaine) did not or only slightly phase-shift the circadian rhythm.


1981 ◽  
Vol 241 (1) ◽  
pp. R62-R66 ◽  
Author(s):  
H. E. Albers

The circadian wheel-running rhythms of gonadectomized adult male, female, and perinatally androgenized female rats, maintained in constant darkness, were examined before and after implantation of Silastic capsules containing cholesterol (C) or estradiol-17 beta (E). The free-running period of the activity rhythm (tau) before capsule implantation tended to be shorter in animals exposed to perinatal androgen. Administration of C did not reliably alter tau in any group. E significantly shortened tau in 100% of females injected with oil on day 3 of life. In females, injected with 3.5 micrograms testosterone propionate on day 3, and males, E shortened or lengthened tau, with the direction and magnitude of this change in tau inversely related to the length of the individual's pretreatment tau. These data indicate that the presence of perinatal androgen does not eliminate the sensitivity of the circadian system of the rat to estrogen, since estrogen alters tau in a manner that depends on its pretreatment length.


2008 ◽  
Vol 295 (4) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Alaa E. S. Abdel-Razik ◽  
Richard J. Balment ◽  
Nick Ashton

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.


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